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+{
+  "question": [
+    "What is the most cited environmental factor for the onset of asthma.",
+    "What is apoptosis?",
+    "How would one extract the DNA, from say, mammals or plants?",
+    "What is a genetic marker?",
+    "Explain the process of finding a genetic marker followed by a quantitative trait loci."
+  ],
+  "answer": [
+    "Air pollution is the most cited environmental factor for the onset of asthma.",
+    "Apoptosis, also known as cell suicide or programmed cell death, is a biological process in multicellular organisms that allows specific cells to be removed during the development of complex tissues, or potentially dangerous damaged cells to be destroyed for the benefit of the whole organism. It is characterized by a sequence of well-defined events resulting in cell destruction and is necessary for normal cell turnover. It is also essential to various other biological processes.",
+    "For mammals, DNA can be extracted using a DNA Isolation Kit for Mammalian Blood, following the manufacturer's instructions. This process typically involves mixing blood with lysis buffer and Proteinase K, followed by the addition of isopropanol and Inhibitor Removal Buffer. The DNA is then washed, centrifuged, and the supernatant discarded. The remaining pellet, which contains the purified genomic DNA, is diluted in TE buffer.  For plants, the mixed alkyl trimethyl ammonium bromide (MATAB) procedure can be used. This involves grinding plant material in liquid nitrogen, incubating it in extraction buffer, and then purifying it with chloroform:isoamylalcohol. The DNA extracts are then precipitated with isopropanol and resuspended in a buffer. The extracts are further purified on anion exchange columns.",
+    "A genetic marker is a measurable polymorphic sequence of DNA whose chromosomal location is known. They often have no known functional significance but are used as pointers to a particular chromosomal location. They are used to track the inheritance of genes and can be a gene or some section of DNA with no known function.",
+    "The process of finding a genetic marker followed by a quantitative trait loci (QTL) involves several steps. First, a population is developed for genetic mapping. This population can be a segregating population or a permanent population. The population is then genotyped using molecular markers. Next, the population is phenotyped for an interested trait. QTL analysis is then conducted using statistical procedures to find markers linked to the QTL. This involves single-marker regression across all chromosomes, where a hypothetical QTL is evaluated at the location of each marker locus. The significance of that QTL is estimated from a likelihood ratio statistic. A permutation test is then conducted to establish genome-wide significance criteria for the trait. The result is a list of marker loci that show a significant association with the trait. These loci are most likely to be near QTLs. The goal of QTL mapping is to identify regions of the genome that harbor genes relevant to a specified trait."
+  ],
+  "contexts": [
+    [
+      "INTRODUCTION  Asthma is a chronic disease of the airways defined by its symptoms, which include reversible airflow obstruction, inflammation, and bronchial hyperresponsiveness.The ancient Egyptians, Greeks, and Romans made reference to the symptoms of asthma, and today the disease is estimated to affect 235-334 million people worldwide (44,53).",
+      "The atopic triad.Perhaps the most widely recognized pattern of co-occurrence is the one of asthma, atopic dermatitis (eczema), and allergic rhinitis (hay fever), which together are referred to as the atopic triad and characteristically present clinically in a temporal sequence known as the atopic march.Within this sequence, atopic dermatitis is typically the first component to manifest, with approximately 20-30% of individuals with mild disease and 70% of those with severe disease going on to develop asthma.Individuals who undergo this distinctive sequence of disease progression frequently exhibit a more severe and persistent phenotype, with increased risk of allergen sensitization.",
+      "Clinically, asthma is characterized by episodes of coughing, chest tightness, wheezing, dyspnea, or sputum production.Often, asthma sufferers experience a combination of these symptoms, or some symptoms more than others.Pulmonary breathing tests typically demonstrate variable airway obstruction and hyperreactivity, but may be normal, even in patients with severe and uncontrolled disease [8].Thus, the diagnosis of asthma, which is based on general clinical symptoms and variable lung function testing, is non-specific and heavily dependent on clinical history.Within the \"umbrella\" diagnosis of asthma there exists a diverse array of differing clinical phenotypes [9].For example, childhood asthma is often associated with personal and parental atopic diseases (i.e., atopic dermatitis, food allergy, eosinophilic esophagitis, allergic rhinitis), viral infections, and tobacco smoke exposure [10].Alternatively, adult-onset asthma is less associated with atopic disease [11,12], but more associated with female sex [13], sinus disease [14], and preceding respiratory infections such as pneumonia [15].In addition, adult-onset disease is often of higher severity [12,16] with a faster and more persistent decline in lung function [17].Moreover, although severe patients are found in every demographic and age group, the most common phenotype is an adult female that is older and obese [18].",
+      "Introduction  An estimated 9% of children and 6% of adults in the United States have asthma [1].The total number of asthma sufferers worldwide is estimated to be over 300 million, with an additional 100 million expected to develop asthma by 2025 [2][3][4][5].Developed countries are the most affected, with some of the highest rates found in the United Kingdom, Australia, New Zealand and the Republic of Ireland [3].Asthma prevalence is rising significantly in developing countries in transition to a more Western lifestyle [3].In 2007, the cost of disease in the United States was estimated to be $56 billion in relation to medical expenses, missed days of work, and early deaths [1].The rate of asthma deaths has likely plateaued, but is still as high as 250,000 per year worldwide [6].Morbidity and mortality are particularly high in ethnic minorities living below or near the poverty line, and African American children had a death rate 10 times that of non-Hispanic white children in 2015 [7].Thus, asthma is a costly, growing health problem associated with high morbidity and mortality.",
+      "Getting accurate estimates of exposures is difficult, whether this is air pollution or toxins in our food and drink, but these are important questions. Rutter: That is an important point. From the twin study data it is clear that environmental effects account for quite a lot of the variance on all the multifactorial disorders. Yet the kinds of measures that are used aren\u2019t terribly solid. They include broad thing such as socio-economic status (SES). Even where there are good measures the care taken in testing for environmental mediation is usually poor.",
+      "Bronchiolitis, a disease that happens in the first year of life in many infants, is strongly associated with subsequent asthma. We ascertained it in the first years of life and have been following these people to age 25 now. For the people who had bronchiolitis and now have asthma, their parents recall much better that they had bronchiolitis than those who don\u2019t have asthma now. It is at least twice more. Extraordinarily, some of these latter parents don\u2019t recall that they took their child to the doctor in the fi rst year of life.",
+      "If you arrive in the USA when you are young you have almost the same prevalence of asthma as an adult as those who are born in the USA and who are not Mexican. But if you arrive at older ages you have less asthma. If you arrive at the age of 20 you have the same asthma risk as those born in Mexico (Eldeirawi et al 2005). Kotb: This is extremely interesting. There is a relationship between depression and the immune system. This especially applies to natural killer (NK) cells, which are the main cells that fight cancers.",
+      "A colleague of mine in Georgia found this may have a protective effect against later development of asthma (Ownby et al 2002). Martinez: We find significantly decreased likelihood of asthma if you have a dog in a home, but not if you have a cat. The reason for this is not that I hate cats, which I do, but most likely because cats are stealth hunters, and they have to be very clean. Dogs are collective hunters and they don\u2019t care if they smell.",
+      "; Guffey, S.E. Investigation into pedestrian exposure to near-vehicle exhaust emissions. Environ. Health 2009, 8, 13. [CrossRef] [PubMed] Our World in Data.org. 2017. Available online: https://ourworldindata.org/data-review-air-pollution-deaths (accessed on 10 January 2022). Pope, C.A. , III. Respiratory disease associated with community air pollution and a steel mill, Utah Valley. Am. J. Public Health 1989, 79, 623\u2013628. [CrossRef] [PubMed] Pope, C.A. , III. What do epidemiologic findings tell us about the health effects of environmental aerosols? J. Aerosol. Med. 2000, 13, 335\u2013354. [CrossRef] [PubMed] Pope, C.A. , III.",
+      "Case for Support BBSRC Grant Application September 2005 \u201cIntegrative Analysis of the Genetic Factors behind Asthma and Atopic Dermatitis\u201d  Part I: Research Proposal Background A Introduction of topic of research and its academic and wider context Asthma is the most common disease of childhood, and affects one child in seven in the United Kingdom. Atopic Dermatitis (AD, eczema) affects similar numbers of children. About 60% of children with severe AD will have concomitant asthma. Treatments for both diseases are unsatisfactory. Abandonment of orthodox medical therapy for AD is common in many families who have children with the disease.",
+      "This is most common during the rainy season when aerosols are created, which results in repeated inhalation of Bp [43, 44]. Environmental sampling studies reveal there is a positive association between the prevalence of disease and the degree of environmental contamination [7]. In addition to environmental factors, data suggests that host factors play an important role in mounting an immune response against infectious diseases [45] such as melioidosis. While healthy persons can contract melioidosis, most patients in endemic regions have an underlying predisposition [28], which suggests that the immunological status of the patient can influence disease initiation and progression [15].",
+      "Sensitivity analysis  We did two sets of post-hoc sensitivity analyses to assess the effects of potential poor recall of age of onset among individuals with adult-onset asthma, and the effects of misclassification of COPD as asthma among the adultonset cases, even with exclusion of cases with a reported diagnosis of COPD, emphysema, or chronic bronchitis.First, to assure that the adult-onset cases did not include a significant proportion of childhood-onset asthma in which symptoms remitted in early life but then relapsed in adulthood, we replaced adult-onset cases with increasing proportions of randomly selected childhood-onset cases, and then tested for association at the two most significant childhood onset-specific loci.This procedure was repeated 20 times for each proportion to quantify the sampling variability (appendix pp 7-8).Second, we did two analyses in which we removed either individuals with ages of asthma onset between 46 and 65 years or adult-onset cases and controls with FEV\u2081/FVC <0\u202270.For each, we compared p values and ORs with the GWAS including all adult-onset cases (appendix pp 8-9).",
+      "We used data for British white individuals from UK Biobank data release July 19, 2017. 8We extracted disease status (asthma, allergic rhinitis, atopic dermatitis, food allergy, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis), age of on set of asthma, and sex from self-reported question naires and hospital records (International Classification of Diseases 10th revision [ICD-10] codes) by querying our in-house protected UK Biobank database server. 9For our main case analysis, we included individuals who self-reported that they had doctor-diagnosed asthma.Further details of our research approach are provided in the appendix (pp 4-7).",
+      "; Guffey, S.E. Investigation into pedestrian exposure to near-vehicle exhaust emissions. Environ. Health 2009, 8, 13. [CrossRef] [PubMed] Our World in Data.org. 2017. Available online: https://ourworldindata.org/data-review-air-pollution-deaths (accessed on 10 January 2022). Pope, C.A. , III. Respiratory disease associated with community air pollution and a steel mill, Utah Valley. Am. J. Public Health 1989, 79, 623\u2013628. [CrossRef] [PubMed] Pope, C.A. , III. What do epidemiologic findings tell us about the health effects of environmental aerosols? J. Aerosol. Med. 2000, 13, 335\u2013354. [CrossRef] [PubMed] Pope, C.A. , III.",
+      "8 The socio-ecologic framework posits that various aspects of a child\u2019s environment directly and indirectly impact the child\u2019s health and development.9 Drawing on this framework, Beck and colleagues10 examined several biologic, social and ecologic variables to provide a greater understanding of factors influencing asthma-related hospital readmissions for black children compared to their white counterparts. The study revealed that black children were over two times as likely to be readmitted for an asthma-related illness compared to white children; this resulted from significant differences in almost every socio-ecologic variable measured, including disease management practices and access to primary care.",
+      "Specific Aims Asthma is the most common chronic pediatric medical condition in the United States, with a prevalence over 9.6% in children under 18 years of age.1, 2 Low-income, urban children incur a disproportionate share of asthma prevalence and morbidity;2-4 13% of children living below the poverty threshold are diagnosed with asthma compared to 8% of non-poor (>200% poverty),3 and poverty is associated with higher rates of asthma attacks.1 Living in an urban area confers additional risk for asthma and increased ED utilization.4, 5 Implementation of the National Asthma Education and Prevention Program\u2019s (NAEPP) Guidelines has contributed to reductions in asthma morbidity and mortality rates, and these guidelines emphasize establishing a partnership between healthcare providers and patients/families to promote effective asthma management.6 The NAEPP expert panel states, \u201cbuilding a partnership requires that clinicians promote open communication and ensure that patients have a basic and accurate foundation of knowledge about asthma\u2026\u201d (p.124),6 yet care partnerships also require that the patient/parent effectively communicate issues such as emerging symptoms or response to medications.",
+      "Vital & health statistics Series 3, Analytical and epidemiological studies. 2012(35):1-58. CDC. Current Asthma Prevalence. https://www.cdc.gov/asthma/most_recent_data.htm. 2015. Updated June 2017. Accessed March 9, 2018. Northridge J, Ramirez OF, Stingone JA, Claudio L. The role of housing type and housing quality in urban children with asthma. Journal of urban health : bulletin of the New York Academy of Medicine. 2010;87(2):211-224. Flores G, Snowden-Bridon C, Torres S, et al. Urban minority children with asthma: substantial morbidity, compromised quality and access to specialists, and the importance of poverty and specialty care.",
+      "Asthma Prevalence and Disparities Asthma is the most common chronic pediatric medical condition in the United States,1 affecting an estimated 6.2 million children annually.2 Poorly controlled pediatric asthma contributes to over 700,000 visits a year to emergency departments (ED).1 Children living in impoverished, urban settings are disproportionately affected by asthma,3 and the disparate impact of asthma is even worse among black and Latino children, and children whose parents have limited English proficiency (LEP) in these urban low-income areas.4-6 A 2017 longitudinal study revealed that black race and Latino ethnicity are significantly associated with worse asthma outcomes including 1) asthma knowledge, 2) asthma-related quality of life, 3) asthma severity, and 4) asthma control.",
+      "The Journal of asthma : official journal of the Association for the Care of Asthma. 2017:16. Inkelas M, Garro N, McQuaid EL, Ortega AN. Race/ethnicity, language, and asthma care: findings from a 4-state survey. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2008;100(2):120-127. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 2007. Publication no. 08-045.1. NIH Consensus Group. Video report: What is mHealth?",
+      "Contact PD/PI: Coker, Tumaini Rucker  INTRODUCTION TO APPLICATION Research Plan Overview Childhood asthma is the most common pediatric medical condition in the United States, and disproportionately affects children living in low-income, urban settings. Many low-income, urban families rely on emergency department (ED) services as their source for sick care for their child. This is often due to not having a primary care provider or sufficient access to their primary care provider for asthma management."
+    ],
+    [
+      "Apoptosis, or controlled cell death [62], is another major stressed-cell response, and was also represented in our results (Fig. 9e).A large body of direct evidence points to apoptosis as one of the main routes of RPE degeneration in AMD [63].Induction of apoptosis upon stress is dictated by the action of master regulator p53, and it was recently shown that aging increases the activity of p53 in RPE cells and the likelihood for apoptotic cell death [64].Consistent with this evidence, we found association with pathways in Transcriptional regulation by TP53 group (Fig. 9d).In particular, Regulation of TP53 activity through methylation was among the top pathway in our association analysis (Table 1), suggesting that p53 modification by methylation and the closely related histone modifications [Protein lysine methyltransferases (PKMTs) methylate histone lysine in Fig. 9e] play important roles in RPE apoptosis regulation.In the intrinsic apoptotic pathway induced by oxidative stress, cytochrome c is released from mitochondria into the cytosol, binding and activating caspases, the main proteases central to apoptotic action.We found association in pathways involving 'inhibitor of apoptosis' (IAP) and its negative regulator 'second mitochondrial activator of caspases' (SMAC) [65], which suggests that disruption to regulatory mechanisms preventing apoptosis in RPE cells may play roles in AMD.",
+      "Apoptosis  Persistent DNA damage",
+      "42 ABSTRACT 18 A MODULARIZED MODEL OF APOPTOSIS HA Harrington, KHo, Sk Ghosh, KC Tung , CY Kao, and B Aguda Imperial College London, Courant Institute of Mathematical Sciences New York University, University of Texas at Arlington, University of Texas Southwestern Medical Center, Mathematical Biosciences Institute, and Department of Mathematics, The Ohio State University Columbus, OH, USA Background: One of the key physiological mechanisms employed by the cell (during development and for maintenance of homeostasis) in multi-cellular organism is apoptosis, which is characterized by a sequence of well-defined events resulting in cell destruction.",
+      "14 Apoptosis is caused by the activation of the caspase cascade, which is initiated by two signaling routes (stress-induced death and death-domain receptor-induced death) (Domen 2001). This process can be prevented by antiapoptotic molecules, such as Bcl-2 (Domen and Weissman 2000). Direct evidence for the involvement of apoptosis in HSC number regulation came from the findings that overexpression of the anti-apoptotic gene bcl-2 led to increased numbers of Thy-1.1low, Sca-1+, c-kit+, Lin- cells, a population with long-term multi-lineage repopulation potential (Domen et al. 2000).",
+      "Several lines of evidence have indicated that apoptosis acts as an important regulator of stem cells. First of all, expression of some apoptosisrelated genes were detected in human and/or murine HSCs (Domen 2001). Secondly, targeted disruption of some of these genes in null and dominant negative mutant mice interfered with normal apoptotic processes in HSCs. For example, overexpression of Bcl-2, a negative regulator of apoptosis, increased not only the numbers and competitive repopulation capabilities of HSCs, but also the resistance of HSCs to apoptosis induced by ionizing radiation (Domen and Weissman 2003).",
+      "Apoptosis  Cell suicide, or apoptosis, is a well-studied biological phenomenon in multicellular organisms that allows specific cells to be removed during the development of complex tissues, or potentially dangerous damaged cells to be destroyed for the benefit of the whole organism.The lack of an apparent evolutionary benefit for such a process in a single-celled organism initially caused controversy about the presence of an apoptotic pathway in yeast.Today, however, a number of yeast orthologues to mammalian apoptosis genes have been discovered and apoptotic-like cell death has been linked to mating, colony formation, and aging (Buttner et al. 2006;Eisenberg et al. 2007;Frohlich et al. 2007).With respect to aging, both replicatively and chronologically aged cells that die have increased ROS and display apoptotic phenotypes (Fabrizio et al. 2004a;Herker et al. 2004;Laun et al. 2001).",
+      "The importance of apoptosis in yeast aging has yet to be fully characterized.At the very least, yeast apoptosis provides a useful pathway for studying genetic interactions for age-related diseases that affect humans, such as cancer.Readers interested in further information related to yeast apoptosis are referred to several in-depth reviews (Buttner et al. 2006;Eisenberg et al. 2007;Frohlich et al. 2007).",
+      "Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 182: 1545-56. Mathew CG (2006). Fanconi anaemia genes and susceptibility to cancer. Oncogene 25: 5875-84. McBride MW, Carr FJ, Graham D, Anderson NH, Clark JS, Lee WK et al (2003). Microarray analysis of rat chromosome 2 congenic strains. Hypertension 41: 847-53. Merino-Trigo A, Kerr MC, Houghton F, Lindberg A, Mitchell C, Teasdale RD et al (2004).",
+      "When a cell harbors such severe DNA damage that it is beyond repair, it is disposed of through apoptosis.Alternatively, DNA damage can induce cellular senescence, the irreversible cessation of mitosis.Both processes are critically dependent on p53, which is known as the guardian of the genome [3] .DNA damage may also trigger autophagy, a cellular catabolic process that maintains homeostasis [4] .It should be noted that under normal conditions cells are rarely exposed to very high doses of DNAdamaging agents, which may be the explanation why we do not age and die because we run out of cells.However, aging is associated with some atrophy [1] and it is conceivable that at older ages bursts of DNA damage, for example from free radical reactions associated with inflammation, do occur and give rise to an increasingly high rate of apoptosis or cellular senescence.While there is some evidence for increased apoptosis and cellular senescence at old age, it is doubtful that under normal conditions this would lead to a significant loss of functional cells.",
+      "Apoptosis, or programmed cell death, literally eliminates cells at risk for neoplastic transformation.Senescence, by contrast, permanently arrests their growth.Both processes are controlled by the p53 tumor suppressor protein (Amundson, Myers, & Fornace, 1998;Bringold & Serrano, 2000;Hickman, Moroni, & Helin, 2002;Itahana, Dimri, & Campisi, 2001).p53 is a transcriptional regulator that both transactivates and transrepresses target genes in response to stress (Prives & Hall, 1999;Ryan, Phillips, & Voudsen, 2001).These target genes, in turn, stimulate DNA repair, transient cell cycle arrest, permanent cell cycle arrest (senescence) or cell death (apoptosis), depending on cell type, degree and type of damage, and other variables.In contrast, cells that lack normal p53 regulation or function -for example, tumor cells -tend to die in response to telomere dysfunction.Some normal human cells, on the other hand, undergo a senescence growth arrest.In either case, when present, p53 is crucial for mediating the cellular response to telomere dysfunction (Yaswen & Stampfer, 2002) (Fig. 4).",
+      "Cell death, and in particular apoptosis, can be caused by a number of mechanisms including loss of growth factors and excitotoxicity (e.g. , Bhutta and Anand, 2002; Nikolic\u0301 et al. , 2013). It is of interest therefore, that proximal to the region of the QTL there are several genes that are related to growth factors including the latent transforming growth factor protein 2 (ltbp2), placental growth factor (pgf), and transforming growth factor beta (Tgf beta).",
+      "Apoptosis-related gene expression profiles",
+      "Apoptosis.Programmed death of cells during embryogenesis and metamorphosis or during cell turnover in adult tissues.",
+      "14 Apoptosis is caused by the activation of the caspase cascade, which is initiated by two signaling routes (stress-induced death and death-domain receptor-induced death) (Domen 2001). This process can be prevented by antiapoptotic molecules, such as Bcl-2 (Domen and Weissman 2000). Direct evidence for the involvement of apoptosis in HSC number regulation came from the findings that overexpression of the anti-apoptotic gene bcl-2 led to increased numbers of Thy-1.1low, Sca-1+, c-kit+, Lin- cells, a population with long-term multi-lineage repopulation potential (Domen et al. 2000).",
+      "Several lines of evidence have indicated that apoptosis acts as an important regulator of stem cells. First of all, expression of some apoptosisrelated genes were detected in human and/or murine HSCs (Domen 2001). Secondly, targeted disruption of some of these genes in null and dominant negative mutant mice interfered with normal apoptotic processes in HSCs. For example, overexpression of Bcl-2, a negative regulator of apoptosis, increased not only the numbers and competitive repopulation capabilities of HSCs, but also the resistance of HSCs to apoptosis induced by ionizing radiation (Domen and Weissman 2003).",
+      "Fraction of cells displaying apoptosis",
+      "It has been known that mitochondria play a central role in the life and death of cells (Kroemer & Reed, 2000).Apoptosis was observed in developmentally arrested embryos by 72 h, but not at 24 h after FCCP treatment, despite considerable telomere attrition at this early stage, suggesting that telomere attrition occurs prior to apoptosis and may serve as an intermediate step between mitochondrial dysfunction and apoptosis.These results also suggest that telomere shortening may signal apoptosis (Lee et al ., 1998;Karlseder et al ., 1999).",
+      "Cell Death  A form of programmed cell death, apoptosis is necessary for normal cell turnover and is essential to a plethora of other biological processes.Apoptosis can be executed via Bcl-2 activation of caspases, via signals from the death receptor on the plasma membrane, or via induction by granzyme B secreted from cytotoxic T cells (Tc cells) [35].Endonucleases and proteases are activated by active caspases, eventually leading to the death of the cell.With age, however, apoptotic activity changes.In heart [36], kidney [37], skeletal muscle [38], and Tc cells [39], increased apoptosis has been reported, perhaps contributing to loss of cellularity in these tissues.This escalation across various tissues may be attributed to the increased production of free radicals [40] and furthermore exacerbated by the accumulation of DNA damage in the aged cells [41].As the risk increases for cells to turn cancerous and dysfunctional with advancing age, increased apoptosis in aged cells is argued to be a defense strategy.In other tissues, such as the colon, apoptosis appears to decrease with age perhaps contributing to the accumulation of senescent cells and age-associated carcinogenesis [42].",
+      "The regulation and execution of apoptosis in endothelial cells is a complex process involving paracrine factors, membrane receptors, interaction of pro-and anti-apoptotic factors and cysteinyl aspartate-specific proteases (caspases).Recent studies suggest that in aging there is an imbalance in the expression of pro-and anti-apoptotic genes resulting in an enhanced apoptosis in the myocardium (19), central nervous system (24), skeletal muscle (10), lung (33), and liver (2,33).Yet, age-related alterations in the expression of pro-and anti-apoptotic genes in coronary arteries have not been elucidated.",
+      "Apoptosis modulating genes  Apopotosis or programmed cell death is associated with alterations in cell morphology, particularly the nucleus, with endonucleatytic cleavage of DNA into nucleosomal length fragments.Apoptosis may result from withdrawal of growth signals."
+    ],
+    [
+      "DNA and RNA extraction of tissues  Genomic DNA was extracted from frozen placentae (n \u03ed 3/group) and liver (n \u03ed 9/group) using a modified version of an established protocol (28,29).Total RNA was extracted from the remaining tissue using TRIzol, as per the manufacturer's instructions (Invitrogen Canada Inc).Genomic DNA and RNA purity and concentration were assessed using spectrophotometric anal-ysis, and integrity was verified using agarose gel [1% (wt/vol)] electrophoresis.",
+      "Taxon Sampling and DNA Extractions  We extracted DNA from 72 pinned specimens from the National Museum of Natural History (NMNH) Entomology collection for this study.We plucked middle legs from the pinned bees using a pair of sterilized forceps and washed the tissue in 95% ethanol to remove dust, pollen, and other forms of accumulated debris on the bee legs.After evaporation of the ethanol (by drying the tissue on a clean Kimwipe \u2122 ), the samples were placed in a freezer for several hours.DNA was then extracted destructively by grinding the frozen tissue with a sterile pestle, using a DNeasy Blood and TissueKit (Qiagen, Valencia, CA, USA) and following the manufacturer's protocol, except the DNA was eluted in 130\u03bcL ddH 2 O instead of the supplied buffer.We ran 10\u03bcL of each extract for 60 min at 100 volt on 1.5% agarose SB (sodium borate) gels, to estimate size of the genomic DNA.",
+      "DNA extraction  DNA was extracted from PBMCs using the QIAamp DNA Mini kit (Qiagen, CA, USA), following the manufacturer's instructions for the spin protocol.The DNA was eluted in 60 \u03bcl of AE elution buffer and stored at -20\u00b0C.The concentration and quality of the DNA was assessed with the Qubit dsDNA HS Assay (Invitrogen, Eugene, OR, USA).",
+      "Methods  Laboratory procedures.We initially screened 107 ancient samples (Supplementary Data 1) in dedicated clean facilities at the ancient DNA lab of Jilin University, China, following published protocols for DNA extraction and library preparation 36,37 .Prior to sampling, we wiped all skeletal elements with 5% bleach and irradiated with UV-light for 30 min from each side.We drilled teeth to obtain fine powder using a dental drill (Dremel, USA).We sampled the dense part of petrous bones around the cochlea by first removing the outer part using the sandblaster (Renfert, Germany), and then grinding the clean inner part into fine powder with the mixer mill (Retsch, Germany).We digested the powder (50-100 mg) in 900 \u03bcl 0.5 M EDTA (Sigma-Aldrich), 16.7 \u03bcl of Proteinase K (Sigma-Aldrich), and 83.3 \u03bcl ddH 2 O (Thermo Fisher, USA) at 37 \u00b0C for 18 h.Then we transferred the supernatant to a MinElute silica spin column (QIAGEN, Germany) after fully mixed with the 13 ml custom binding buffer [5 M guanidine hydrochloride (MW 95.53), 40% Isopropanol, 90 mM Sodium Acetate (3 M), and 0.05% Tween-20] followed by two washes with PE buffer (80% ethanol).Then we eluted the DNA with 100 \u03bcl TET buffer (QIAGEN, Germany).",
+      "DNA Extraction  After blood was drawn into EDTA tubes, genomic DNA was extracted using a DNA Isolation Kit for Mammalian Blood Kit (Roche Applied Science, Indianapolis, IN, USA) according to the manufacturer's recommendations.Briefly, 300 \u03bcl of whole blood from each sample was mixed with 200 \u03bcl of lysis buffer (50 mM Tris pH 8.0, 100 mM EDTA, 100 mM NaCl, 1% SDS) and 40 \u03bcl of Proteinase K, followed by addition of 100 \u03bcl of isoproponal and 500 \u03bcl of Inhibitor Removal Buffer (5M guanidine-HCl, 20 mM Tris-HCl pH 6.6).The DNA was washed with a buffer (20 mM NaCl; 2 mM Tris-HCl; pH 7.5), centrifuged twice at 2000 rpm, washed using cold 70% ethanol and centrifuged at 3000 rpm.The supernatant was discarded and the pellet containing purified genomic DNA was diluted in TE buffer (1 mM EDTA; 10 mM Tris-HCl, pH 7.5) to a concentration of approximately 50 ng/\u03bcl.",
+      "Genomic DNA extraction  Leukocytes were isolated from 5-ml peripheral blood samples.DNA was prepared by phenol extraction and chloroform extraction followed by isopropanol precipitation, washed with ethanol, and air-dried.Tris-EDTA buffer pH 8.0 was used to dissolve the final genomic DNA product.",
+      "The pulled down DNA fragments were extracted and purified using phenolchloroform extraction/ethanol precipitation.The samples were stored at -20 \u00b0C until use.",
+      "DNA extraction for genotyping  For the majority of samples, DNA was extracted from either spleen or the exocrine fraction of the islet isolation using the Tissue DNA Purification Kit according to manufacturer's instructions on an automated Maxwell 16 system (both Promega, USA).When no other tissue was available, DNA was extracted from human islets using the Trizol fraction remaining after extraction of RNA (see above).To precipitate the DNA, 300\u03bcl 100% ethanol was added to the thawed solution.This mixture was incubated at room temperature for a minimum of 30 minutes.DNA was then pelleted by centrifugation at 4,000 x g for 5 minutes at 4\u00b0C.After removing the supernatant, the pellet was twice washed with 0.1M trisodium citrate (Sigma Aldrich, UK) in 10% ethanol and left at room temperature for 30 minutes, followed by another wash step with 75% ethanol.After the final wash step, pellets were air-dried for 10 minutes to remove residual ethanol and re-suspended in a minimum of 100 \u03bcL 8mM NaOH (Sigma Aldrich).Extracted DNA was stored at -20\u00b0C before further use.",
+      "DNA extraction  Tissue samples were incubated at 50\u00b0C overnight with shaking in DNA extraction buffer (100 mM NaCl, 10 mM Tris.HCl pH8, 25 mM EDTA, 0.5% (w/v) SDS), containing 200 \u03bcg/ml proteinase K. DNA was isolated by two rounds of phenol:chloroform extraction, followed by RNAse A treatment, precipitation in absolute ethanol containing 10% (v/v) sodium acetate (3 M, pH 5.2), and resuspended in 100 \u03bcl nuclease-free water (Ambion, Austin, TX, USA) or using salting out method followed by purification with Qiagen blood and tissue kit (Qiagen, Mississauga, ON, USA).DNA was stored at -20\u00b0C.",
+      "Methods  Human DNA samples DNA was extracted from human patient tissue samples acquired from the University of Minnesota Tissue Procurement Facility from BioNet (IRB#0805E32181).See Supplemental Table S4 for patient data.Briefly, 2 mg of tissue was digested overnight at 55\u00b0C on a rotating platform in 710 mL of digest buffer (1 M Tris at pH 8.0, 1 mM EDTA, 13 SSC, 1% SDS, 1 Mm NaCl, 10 mg/mL Proteinase K).Following digest, DNA was purified using phenolchloroform-isoamyl alcohol (Life Sciences) isolation protocol.",
+      "3.2.2 Isolation of genomic DNA Genomic DNA was isolated from frozen liver tissue. The isolation was conducted using the Qiagen DNeasy\uf8e8 Blood & Tissue Kit (Qiagen) according to the manufacturer\u2019s protocol. DNA concentration was evaluated photometrically at a wavelength of 260 nm using the FusionTM Universal Microplate Analyzer. For nucleic acid quantification, the Beer-Lambert (A = \u03b5 * b * c) equation is modified to use an extinction coefficient with units of M-1 cm-1.",
+      "Most typically, DNA is extracted from blood samples, dried blood spots, buccal swabs, saliva, tissue and even urine and stool samples.In forensic science, other sources have been validated e.g.bone, tooth pulp, dandruff and others.",
+      "DNA isolation  High-molecular weight DNAs was isolated from the samples by organic solvent extraction method, followed by precipitation in cold ethanol [14].",
+      "Genomic DNA extraction  DNA from MEF cultures or mouse liver was isolated by phenol/chloroform extraction, as described [11].",
+      "DNA is usually recovered from cells by methods that include cell rupture but that prevent the DNA from fragmenting by mechanical shearing. This is generally undertaken in the presence of EDTA, which chelates the magnesium ions needed as cofactors for enzymes that degrade DNA, termed DNase. Ideally, cell walls, if present, should be digested enzymatically (e.g. , lysozyme in the bacteria or bacterial cell). In addition the cell membrane should be solubilized using detergent.",
+      "DNA solutions can be stored frozen, although repeated freezing and thawing tends to damage long DNA molecules by shearing. A flow diagram summarizing the extraction of DNA is given in Fig. 1.2. The above-described procedure is suitable for total cellular DNA. If the DNA from a specific organelle or viral particle is needed, it is best to isolate the organelle or virus before extracting its DNA, because the recovery of a particular type of DNA from a mixture is usually rather difficult.",
+      "Genomic DNA extraction  Genomic DNA was extracted by the mixed alkyl trimethyl ammonium bromide (MATAB) procedure.Briefly, 250 mg of plant material was ground in liquid nitrogen and immediately incubated in 2 ml of pre-warmed extraction buffer (100 mM Tris-HCl, pH 8, containing 20 mM EDTA, 1.4 M NaCl, 2% (w/v) MATAB, 1% (w/v) PEG6000 (polyethylene glycol), 0.5% (w/v) sodium sulfite, 20% (w/v) Igepal CA630, 20% (w/v) lithium dodecyl sulfate, and 20% (w/v) sodium deoxycholate) at 74 \u00b0C for 20 min.After purification with 2 ml of chloroform:isoamylalcohol (24:1, v/v), DNA extracts were precipitated with 1.6 ml of isopropanol then resuspended in 1 ml of buffer (50 mM Tris-HCl, pH 8, containing 10 mM EDTA and 0.7 M NaCl).The extracts were purified on anion exchange columns (QIAGEN-tip 20) following the manufacturer's instructions (QIAGEN, Valencia, CA).",
+      "DNA extraction and enzymatic digestion  Total DNA was isolated from whole blood and separated blood subtypes using a Qiagen DNeasy Blood & Tissue Kit following the manufacturer instructions.After extraction, DNA was quantified by NanoDrop (Thermo Scientific NanoDrop products, Wilmington, DE).The isolated genomic DNA was enzymatically digested according to previously described method.Briefly, DNA (3 \u03bcg) was first denatured by heating at 95 \u00b0C for 5 min and then chilling on ice for 2 min.Then, 1/10 volume of S1 nuclease buffer (30 mM CH 3 COONa, pH 4.6, 280 mM NaCl, 1 mM ZnSO 4 ) and 100 units of S1 nuclease were added before the mixture (20 \u03bcL) was incubated at 37 \u00b0C for 16 h.Subsequently, after 1/10 volume of alkaline phosphatase buffer (50 mM Tris-HCl, 10 mM MgCl 2 , pH 9.0), 0.002 units of venom phosphodiesterase I, and 10 units of alkaline phosphatase were added, the solution was incubated at 37 \u00b0C for an additional 4 h followed by extraction with an equal volume of chloroform for twice.The aqueous layer was collected and lyophilized to dryness and then reconstituted in 100 \u03bcL water.About 30 \u03bcL of the obtained samples were then subjected to liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis.",
+      "The conventional DNA extraction procedure involved the homogenization of single D. magna in 400 l of sperm lysis buffer (100 mM Tris-HCl, pH 8; 500 mM NaCl; 10 mM ethylenediaminetetraacetic acid [EDTA], pH 8; 1% SDS; 2% mercaptoethanol) followed by RNase treatment (40 g, 37\u040aC for 1.5 h).The DNA was then extracted in phenol (pH 8) and chloroform:isoamyl alcohol (1:1).The DNA was finally precipitated by two volumes of ice-cold ethanol in the presence of 3 M sodium acetate (1/10 of the DNA volume) and was incubated at \u03ea80\u040aC overnight.Precipitated DNA was harvested by centrifugation, dried in air, and the final pellet dissolved in sterile analytic grade water.",
+      "DNA extraction and quantification  DNA was extracted from whole organs by standard techniques (34) with emphasis on minimizing shearing or nicking of DNA as nicked DNA has been shown to be refractory to LX-PCR (35).DNA from the brain was extracted from the right hemisphere.Extracted DNA was resuspended in 10 mM Tris 1 mM EDTA (pH 8) (TE) and stored at 4_C.A number of samples were normalized for mtDNA content by dot blotting and hybridization with digoxigenin-labeled full-length mtDNA and densitometry.In cases where mtDNA quantification was not carried out, the DNAs were normalized by A 260 of total DNA."
+    ],
+    [
+      "Using genetic markers, the pattern of inheritance can be tracked through families. For example, by analyzing a marker linked to the eye color gene in several generations, it is possible to determine from which grandparents a child has inherited its eye color alleles. More importantly, \ufb01nding a marker linked to a disease can lead to location of the faulty gene causing the disease. Finding the gene is very valuable in the search for the cure. The distance between two loci can be expressed either as physical or genetic distance.",
+      "It is well known, however, that not all genomic markers are independent (Frazer et al., 2007).Genetic variation is often inherited in contiguous segments of DNA, such that there tends to be correlation between the inheritance of alleles at markers close to each other on the same chromosome.This genetic correlation is called linkage disequilibrium (LD), and, as a result, the effective number of independent tests (M eff ) conducted is less than the total number of markers (M).By effective number of tests, we mean the number of independent tests that would have to be conducted to lead to a null distribution for the minimum P-values that was approximately the same as that obtained when conducting tests that are necessarily correlated due to LD.",
+      "Genetic mapping is a powerful strategy that exploits genomic information to dissect complex traits into Mendelian loci (quantitative trait loci or QTL) and identifies genetic * Correspondence: marioenrico.pe@sssup.it 1 Institute of Life Sciences, Scuola Superiore Sant\u2019Anna, Pisa, Italy Full list of author information is available at the end of the article  determinants that may lead to crop improvement. As marker density ceases to be a limiting factor [3], our ability to discover specific genetic determinants in a single mapping study depends upon the availability of populations with high genetic diversity and recombination density [4].",
+      "This capacity allows samples to be placed into meaningful genetic groups that reflect evolutionary relationships (more stable, lower diversity markers), while simultaneously permitting high levels of strain resolution (high diversity markers). From a clinical perspective, markers that accurately reflect broad evolutionary relationships are valuable for comparing the genetic similarity of an isolate to isolates on a regional or global scale, whereas high-resolution markers are valuable for detailed epidemiological tracking in an outbreak. Variable-number tandem repeats (VNTRs) are genetic markers that can span a range of variability and, therefore, can capture genetic relationships on multiple scales (18\u201319).",
+      "Identifying the genetic loci that modulate a trait based on correlation between variation in phenotype and variation in genotype is the essence of genetic mapping. This first involves systematically genotyping a genetically diverse population using microsatellite or SNP markers. The phenotype of interest is then measured and its variability in the population assessed. A statistical test is then carried out to identify chromosomal regions that segregate with the trait and show linkage with the trait, i.e. ,  3 identify genetic regions that have the same genotype among individuals with similar trait values but differ between individuals with dissimilar trait values.",
+      "Using genetic markers, the pattern of inheritance can be tracked through families. For example, by analyzing a marker linked to the eye color gene in several generations, it is possible to determine from which grandparents a child has inherited its eye color alleles. More importantly, \ufb01nding a marker linked to a disease can lead to location of the faulty gene causing the disease. Finding the gene is very valuable in the search for the cure. The distance between two loci can be expressed either as physical or genetic distance.",
+      "Genetic variation  For decades researchers used single markers to elucidate clinal differentiation and spatial variation in allele frequencies.This approach revealed multiple markers with variation that tracked the clines, including some with the same allele at higher frequency at the same latitude in the Northern and Southern hemispheres.Examples include alcohol dehydrogenase (Adh), a-glycerol-3-phosphate dehydrogenase (Gpdh), glucose-6-phosphate dehydrogenase (G6pd), esterase-6 (Est-6), octanol dehydrogenase (Odh), and 6-phosphogluconate dehydrogenase (Pgd) [30][31][32][33] (Table 1).Perhaps the most heavily explored locus in D. melanogaster has been Adh, the first step in the ethanol detoxification pathway.The Adh-F allele encodes high catalytic activity of ADH, but this increase in activity trades off with enzyme stability at higher temperatures [34,35].Unsurprisingly, the Adh-F allele is found at a higher frequency in cooler high-latitude populations, and differentiation has occurred in parallel along clines in",
+      "In the case of genetic markers, this easily runs in the several hundreds to thousands. Moreover, the optimal subset of markers is heavily dependent on how these markers are combined, i.e. dependent on the optimal Boolean function . Altogether, one frequently has to rely on greedy search strategies that easily get stuck in local optima or near exhaustive searches that are computationally too expensive, especially when employed in permutation procedures required to assess statistical significance. Our solution to this problem hinges upon two observations.",
+      "GENE MAPPING  The opportunity to merge advances in molecular genetic technology with advances in statistical techniques expanded in earnest with the development of DNA markers such as restriction fragment length polymorphisms (Lander and Botstein, 1989).Research exploded in the past decade with the continued refinement of molecular technology yielding a variety of DNA markers-e.g., short tandem repeats (STRs) or microsatellites; variable number of tandem repeats (VNTRs); single nucleotide polymorpohisms (SNPs), and gene expression microarrays or gene chips.A genetic marker is a measurable polymorphic sequence of DNA whose chromosomal location is known.Markers often have no known functional significance but are used as pointers to a particular chromosomal location.The logic of gene mapping technology is simple: Determine if there is a relationship between variability in a phenotype and variability in an anonymous DNA marker of known chromosomal location.If there is a relationship, it is taken as evidence that there is a gene that influences the trait at or near the marker.",
+      "Genetic drift. Genetic changes in populations caused by random phenomena rather than by selection.Genetic marker.A segment of DNA with an identifiable physical location on a chromosome whose inheritance can be followed.A marker can be a gene, or it can be some section of DNA with no known function.",
+      "Biological characteristics indicating initial resiliency or susceptibility of an organism include genetic profiles.As noted above, genetic markers need to have a high prevalence in the population and have a reasonably strong effect on common population health outcomes, or have an interaction effect with other health-affecting mechanisms, to be candidates for inclusion in population studies.At the moment, the only known genetic marker of clear value in a population survey is the apolipoprotein E gene (APOE), although this is likely to change in the very near future.APOE allele status is clearly related to a number of major health outcomes in older populations which are reasonably well measured in population surveys: mortality, heart disease, and cognitive functioning (Albert et al., 1995b;Corder et al., 1993;Evans et al., 1997;Ewbank, 1997;Hofman et al., 1997;Hyman et al., 1996;Luc et al., 1994;Saunders et al., 1993).Both the prevalence of alleles indicating higher risk and the size of the effect are large enough to be of importance in explaining variability in currently studied health outcomes.APOE allele status has been shown to have independent effects on health outcomes and to interact with other life circumstances such as sex and race in its effect on health outcomes (Jarvik et al., 1995;Maestre et al., 1995;Payami et al., 1992).Incorporation of information on this genetic indicator could lead to increased knowledge of the interactive mechanisms of this genetic marker and other social and behavioral variables and thus clarify some of the mechanisms leading to population differentials in cognition, heart disease, and mortality.",
+      "As described by Hermalin (1999), if genetic markers are modeled as part of an individual's physiological structure, they can provide controls for predisposing factors that affect more proximate mid-level markers of function as well as downstream health outcomes.This potential benefit of genetic information-i.e., its power in explicating the black box of Figure 11-1-may outweigh, or at least precede, its near-term potential for discovering genetic links to chronic disease.As discussed by Weiss (1998b), the situation with chronic disease differs from single locus disorders that are inherited following well-identified Mendelian rules.In general, we cannot expect to find relationships that are even as straightforward as the APOE links to cardiovascular and Alzheimer's disease.Variation across populations, difficulty in identifying a small enough area on the chromosome to search for disease-associated genes, and the problems inherent in identifying continuous outcomes with particular genes may limit finding the connections.",
+      "This capacity allows samples to be placed into meaningful genetic groups that reflect evolutionary relationships (more stable, lower diversity markers), while simultaneously permitting high levels of strain resolution (high diversity markers). From a clinical perspective, markers that accurately reflect broad evolutionary relationships are valuable for comparing the genetic similarity of an isolate to isolates on a regional or global scale, whereas high-resolution markers are valuable for detailed epidemiological tracking in an outbreak. Variable-number tandem repeats (VNTRs) are genetic markers that can span a range of variability and, therefore, can capture genetic relationships on multiple scales (18\u201319).",
+      "These variations provide a species the ability of adapting to the environment change (Liu and Cordes, 2004). DNA markers are among the most powerful tools for revealing genetic variations in organisms. Historically, many different types of markers have been used for aquaculture studies  Functional Genomics in Aquaculture, First Edition. Edited by Marco Saroglia and Zhanjiang (John) Liu. \u2402 C 2012 John Wiley & Sons, Inc. Published 2012 by John Wiley & Sons, Inc.  41 42  Functional Genomics in Aquaculture  Table 2.1  A summary of characteristics of various molecular markers used in aquaculture species.",
+      "For instance, mapping of a trait or a phenotype would require polymorphic DNA markers such as microsatellites (SSRs) or single nucleotide polymorphisms (SNPs); expression pro\ufb01ling would require genome annotation information; microarray design would require sequence information of genes, etc. The objective of this chapter is to provide a general review of genomic resources needed, and currently present for aquaculture species, for functional genomics studies. Polymorphic DNA Markers The key factor behind the signi\ufb01cant differences at the level of individuals, species, and higher order of taxonomic groups is genetic variation (polymorphism).",
+      "Functional genomics:  The study of genes, their resulting proteins, and the role played by the proteins in the biochemical processes of the body.Gene: A unit of inheritance; a working subunit of DNA.Each of the 20 000 to 25 000 genes in the body contains the code for a specific product, typically a protein such as an enzyme.Gene expression: The process by which the coded information of a gene is translated into the structures present and operating in the cell (either proteins or ribonucleic acids).Gene markers: Landmarks for a target gene, either detectable traits that are inherited along with the gene or distinctive segments of DNA.Gene map: A description of the relative positions of genes on a chromosome and the distance between them.Genetic counseling: A short-term educational counseling process for individuals and families who have a genetic disease or who are at risk for such a disease.Genetic counseling provides patients with information about their condition and helps them make informed decisions.Genetic linkage maps: DNA maps that assign relative chromosomal locations to genetic landmarks-either genes for known traits or distinctive sequences of DNA (ie, genetic markers)-on the basis of how frequently they are inherited together.Genetic testing: Examining a sample of blood or other body fluid or tissue for biochemical, chromosomal, or genetic markers that indicate the presence or absence of genetic disease.Genetics: The scientific study of heredity, how particular qualities or traits are transmitted from parents to offspring.Genome: All the genetic material in the chromosomes of a particular organism.Genome-wide: Descriptor that indicates that the entire breadth of the genome has been examined in a study (eg, a linkage or association study).Genome-wide studies do not resequence the entire genome but type (an increasingly large set of) markers distributed throughout the genome.Genomics: A \"scaled-up\" version of the science of genetics that investigates the structure and function of large sections of the genome simultaneously.Genotype: The actual genes carried by an individual (as distinct from phenotype-ie, the physical, bodily characteristics into which genes are translated).Haplotype: A way of denoting the collective genotype of a number of closely linked loci on a chromosome.Heritability (h 2 ): For any trait, the proportion of the phenotypic variability resulting from genetic variance.Note that heritability does not indicate the degree to which a trait is \"genetic. \"Nor does a high h 2 mean that the trait cannot be influenced by environment.A heritability significantly \u03fe0, however, can provide a rationale for further genetic and genomic study of a trait of interest.Heterozygous: Possessing 2 different sequences (ie, genotypes) of a particular gene, 1 inherited from each parent.High-throughput genotyping: In contrast to the older labor-and time-intensive genotyping methods, high-throughput genotyping makes use of robots, computers, and other evolving technologies, thus enabling laboratories to type up to hundreds of thousands of polymorphisms in many samples in a relatively short period of time.Homozygous: Possessing 2 identical sequences of a particular gene, 1 inherited from each parent.Interaction: The differing effect of 1 independent variable on the dependent variable, depending on the particular level of another independent variable.For example, there would be an interaction between the factors sex and treatment if the effect of treatment was not the same for male and female subjects in a drug trial.Linkage analysis: A gene-hunting technique that traces patterns of heredity in large, high-risk families in an attempt to locate a disease-causing gene mutation by identifying traits that are coinherited with it.Linkage disequilibrium: Two alleles at different loci that occur together on the same chromosome more often than would be predicted by chance alone.It is a measure of cosegregation of alleles in a population.",
+      "Source: Kearsey and Pooni (1996). Genetic maps consist of a series of markers or identifiable features at known, or perhaps best described as estimated, locations on the genome (see Figure 9). For some discrete traits, simple Mendelian inheritance is followed and the phenotype has a one to one correspondence with the genes controlling it. These are so called morphological markers, which were then related to continuous or quantitative traits of interest. Examples are shape, colour, size or height in particular varieties of peas, as studied by Mendel. For another example, see Appendix A.2.",
+      "Genomic markers used in linkage mapping have evolved from restriction fragment length polymorphisms (RFLPs) to microsatellites (simple sequence repeat polymorphisms; SSRPs), to single-nucleotide polymorphisms (SNPs), with the more modern markers exhibiting higher frequencies in the genome (thus ensuring fuller coverage). Linkage mapping of a trait is in fact the demonstration of linkage between the phenotype and a genomic marker, followed by an inference of linkage between the genomic marker and the responsible DNA variant. Transitive logic ties the phenotype with the DNA variant, which is of course the point of the exercise. See Fig.",
+      "However, because of time constraints it is often more practicable to choose an appropriate mapping population that is already available through the current stock centers. Plant species chosen for study will depend largely on the availability of suitable plant resources. Obtain appropriate mapping population information to include information on markers/genotypes (see Note 4). A marker is an identifying factor; a gene or other DNA of known location that is used to track the inheritance and so on of other genes whose exact location is not yet known.",
+      "The closer two genes are together on a chromosome, the  less likely it is for a recombination event to occur between the two, causing a non-random association. This is the basis for genetic linkage. The development of genetic markers allowed the theory of linkage disequilibrium (LD) to be used in mapping genes. Genetic markers are speci c genetic di\u241berences between species or cultivars, and genetic linkage of these markers to particular morphological traits can allow genetic markers to be used to represent the gene of interest (Collard et al. , 2005)."
+    ],
+    [
+      "This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction The association between a complex phenotypic trait and genetic markers on the chromosomes can be detected through statistical analysis, leading to the identification of quantitative trait loci (QTL)\u2014regions of the chromosomes that appear to be associated with the phenotype. Quantitative trait loci (QTL) are expected to be associated with the genes controlling some aspects of the phenotype.",
+      "Nowadays many different cost-efficient genotyping solutions (including sequencing and Single Nucleotide Polymorphisms arrays) have opened the way to systematic genome-wide fine mapping of quantitative traits (Quantitative Trait Locus or QTL mapping). The process of QTL mapping (Figure 1) consists in searching for genome regions that influence the value of a given trait. For example, identifying a QTL for plant height means finding a DNA region at which the plants that carry a certain allele tend to be significantly higher or lower than those carrying another allele.",
+      "QTLs are regions within the genome whose genetic variation modulates quantitatively a phenotype characteristic of the particular trait under study (Lynch and Walsh, 1998). Determining the association between variations in specific disease phenotypes or a trait, with variations in genotypes of a reference population can be used to locate a QTL. One of the methods used for mapping QTLs associated with complex traits is genetic markers-trait association. Genetic markers associated with certain loci can be inherited in linkage disequilibrium. Generating populations with linked loci in disequilibrium is achieved though either crosses between inbred lines, or use of the out-bred populations.",
+      "Often, the first step in analysis of new trait data is single-marker regression across all chromosomes. A hypothetical QTL is evaluated at the location of each marker locus, and the significance of that QTL is estimated from a likelihood ratio statistic (LRS) (Haley and Knott, 1992). For this analysis, WebQTL automatically does a permutation test to establish genomewide significance criteria for the trait (Churchill and Doerge, 1994).",
+      "One possible approach to facilitate this endeavor is to identify quantitative trait loci (QTL) that contribute to the phenotype and consequently unravel the candidate genes within these loci. Each proposed candidate locus contains multiple genes and, therefore, further analysis is required to choose plausible candidate genes. One of such methods is to use comparative genomics in order to narrow down the QTL to a region containing only a few genes. We illustrate this strategy by applying it to genetic findings regarding physical activity (PA) in mice and human.",
+      "Elucidation of the molecular basis of these traits has proven difficult as they are under the control of multiple genes and genetic loci. The standard approach to gene identification involves mapping by linkage analysis in experimental crosses, and this has led to the localization in the rat genome of hundreds of quantitative trait loci (QTLs) underlying trait variation (68). We refer to these loci as physiological quantitative trait loci (pQTLs).",
+      "Often, the first step in analysis of new trait data is single-marker regression across all chromosomes.A hypothetical QTL is evaluated at the location of each marker locus, and the significance of that QTL is estimated from a likelihood ratio statistic (LRS) (Haley and Knott, 1992).For this analysis, WebQTL automatically does a permutation test to establish genomewide significance criteria for the trait (Churchill and Doerge, 1994).By default, it returns a list of marker loci that show greater than sugges-tive association with the trait according to standard criteria (Lander and Kruglyak, 1995), but it will also accept user-defined criteria.Local maxima in the LRS in this list identify loci that are most likely to be near QTLs.WebQTL provides this list within a few seconds.",
+      "QTLs can be identified through their genetic linkage to visible marker loci with genotypes that can be readily classified [94, 97]. As such, markers that are genetically linked quantitative trait will segregate more often with trait values, whereas unlinked markers will lack an association with the phenotype [94, 98]. The principal goal of a QTL analysis is to identify all QTLs linked to a trait and discern whether phenotypic differences are mainly due to a few loci with large effects, or many loci with small effects [98].",
+      "This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction The association between a complex phenotypic trait and genetic markers on the chromosomes can be detected through statistical analysis, leading to the identification of quantitative trait loci (QTL)\u2014regions of the chromosomes that appear to be associated with the phenotype. Quantitative trait loci (QTL) are expected to be associated with the genes controlling some aspects of the phenotype.",
+      "The basic principle of classic QTL is trait segregation along with the markers and necessitated the availability of two or more genetically different lines corresponding with the phenotypic trait. Markers like single nucleotide polymorphisms (SNPs) and microsatellites are used for genotypic distinctions (Vignal et al. , 2002). QTL mapping is achieved in four basic steps; the first one is the measurement of variation for a trait in the individuals. It is a prerequisite to have the traits that show phenotypic variability among the individuals (inbred strains).",
+      "Often, the first step in analysis of new trait data is single-marker regression across all chromosomes.A hypothetical QTL is evaluated at the location of each marker locus, and the significance of that QTL is estimated from a likelihood ratio statistic (LRS) (Haley and Knott, 1992).For this analysis, WebQTL automatically does a permutation test to establish genomewide significance criteria for the trait (Churchill and Doerge, 1994).By default, it returns a list of marker loci that show greater than sugges-tive association with the trait according to standard criteria (Lander and Kruglyak, 1995), but it will also accept user-defined criteria.Local maxima in the LRS in this list identify loci that are most likely to be near QTLs.WebQTL provides this list within a few seconds.",
+      "Often, the first step in analysis of new trait data is single-marker regression across all chromosomes. A hypothetical QTL is evaluated at the location of each marker locus, and the significance of that QTL is estimated from a likelihood ratio statistic (LRS) (Haley and Knott, 1992). For this analysis, WebQTL automatically does a permutation test to establish genomewide significance criteria for the trait (Churchill and Doerge, 1994).",
+      "Quantitative Trait Locus (QTL) mapping To map QTL, we used 934 AXB/BXA genetic informative markers obtained from http://www. genenetwork.org. For all the in vitro measurements and gene expression linkage analysis, a genome-wide scan was performed using R/qtl [57]. Significance of QTL logarithm-of-odds (LOD) scores was assessed using 1000 permutations of the phenotype data [114] and the corresponding p-values reported. For the cellular phenotypes, QTL significance was reported at a genome-wide threshold corresponding to p < 0.05.",
+      "Typically one may obtain a location known to derive from only one of the two parent strains that contains a chromosomal region that correlates with a trait of interest. Since the actual gene and gene product will frequently remain unknown, the region is referred to as quantitative trait locus (QTL), and is simply named for the trait itself (Alberts & Schughart, 2010). Growing sets of strain-dependent marker locations in established RI strains are continually updated in online repositories.",
+      "By definition, a quantitative trait locus is a chromosomal region that contains a gene, or genes, that regulate a portion of the genetic variation for a particular phenotype (Wehner et al. 2001). The goal of QTL mapping is to identify regions of the genome that harbour genes relevant to a specified trait. QTL map locations are commonly determined by initial screening of mice with specific genetic characteristics, such as recombinant inbred strains, the F2 of two inbred strains, or recombinant congenic strains (Flint 2003).",
+      "Often, the first step in analysis of new trait data is single-marker regression across all chromosomes. A hypothetical QTL is evaluated at the location of each marker locus, and the significance of that QTL is estimated from a likelihood ratio statistic (LRS) (Haley and Knott, 1992). For this analysis, WebQTL automatically does a permutation test to establish genomewide significance criteria for the trait (Churchill and Doerge, 1994).",
+      "QTL linkage studies are conducted in order to map a region or regions of the genome which affect a continuous or quantitative trait. In agriculture, as soon as markers linked to QTL are found for economically important traits, these markers can be used for selecting individuals in breeding programmes. In human studies, the aim is often to identify markers indicating disease susceptibility. Current techniques for measuring markers are usually relatively slow and laborious. Newer DNA technology, such as SNP or single nucleotide polymorphisms (Kwok, 2001b; Patil et al.",
+      "Genomic regions linked to complex traits can be identified by genetic mapping and quantitative trait locus (QTL) analysis (Shehzad and Okuno 2014). 7 QTL mapping QTL mapping with molecular markers is the first strategy in genetic studies. In plant breeding, QTL mapping is an essential step required for marker-assisted selection (Mohan et al. 1997; Shehzad and Okuno 2014). The fundamental idea underlying QTL analysis is to associate genotype and phenotype in a population exhibiting a genetic variation (Broman and Sen 2009).",
+      "Four steps of QTL mapping are (1) development a  W  population, (2) genotyping the population using molecular markers, (3) phenotyping the population for an interested trait, and (4) QTL analysis using statistical procedures to find  IE  markers linked to the QTL (Bernardo 2002). PR EV  Populations used for genetic mapping can be a segregating population (F2 and backcross) or a permanent population (double haploids or recombinant inbred lines). Recombinant inbred lines (RILs) are developed by selfing of individual progenies of the F2 plants until homozygosity is achieved (F7-F8).",
+      "This tool allows systems genetic analysis of single genes or small sets of genes using a bottom-up approach. relations define quantitative trait loci (QTLs). Because the marker is not typically the actual site of the polymorphism, interpolative methods have been developed to estimate the distance of the QTL from the marker and the strength of the association. Using multiple-regression and model-fitting methods, the true complexity of the phenotypic variation can be modeled through the consideration of multiple loci and environmental factors as predictors [13]."
+    ]
+  ]
+}
\ No newline at end of file