GWAS Essay

GWAS Essay
The analysis article is based on the Genome–wide association studies of cancer, or
GWAS. GWAS is an approach to research the genetic basis of different diseases. For
example, with oncology, GWAS was performed and able to identify approximately 450 genetic
variants that are related to the risks, as well as provided proof of polygenic susceptibility.
This review targeted on the functional basis and gene structure of cancer susceptibility.
Regarding cancer, there's a pattern of relative risk or RR, that's high in relatives of patients who experienced early–onset cancer. Some risks in
first–degree relatives of patients accrued from twofold to threefold. Leukemia and testicular cancers are exceptions where the RR were accrued from ...
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There were two classes of cancer susceptibility variants identified. First one was the rare–moderate penetrance variants that were known through the
candidate genes, which had a risk allele frequency of less than 2%. An example of this would be when other genes encoded proteins in the DNA
damage, which is associated with breast cancer risk. The second one would be the common low–penetrance alleles, which had risk allele frequency less
than 5%. This reflected upon the various subgroups of risk alleles that were detected. GWAS compared the frequency of common DNA variations with
healthy individuals. Figure 2 showed the performance of DNA samples that were taken. The controls and patients' DNA samples were genotyped using
genome platforms that analyzed genetic variations in single nucleotide polymorphisms (SNPs). There should be a match between the patients and
controls to attenuate the false–positive associations. To minimize them, statistical thresholds like Bonferroni correction is used. Bonferroni correction is
a common threshold for genome–wide significance of a P–value that is less than 0.00000005, or a 5% significance level for millions of tests. The
threshold is used for sequencing studies or genome imputation of ten million variants, assuming that linkage disequilibrium would be equivalent to a
million independent tests. Also, the imputation of genotypes by sequenced panels
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What Is A Gene?
What is a gene?
The word Gene derives from the Greek "genesis" (birth) or "genos" (origin) and was first coined by Wilhelm Johannsen in 1909. At that time, little or
nothing was known about the existence of DNA, and the word gene was used to describe the Mendelian concept of a phenotypical trait that is
transmitted through inheritance (Johansen, 1909).
The gene as the fundamental unit of heredity is the original meaning of the word as first geneticists intended it. This essentially explains the reason
why, during last century, a burst of research occurred in the genetic field: it was carried out in order to discover the genes responsible for the most
various traits, from the ones causing diseases to the ones responsible for genetic variation across populations. In fact, the scientific community was
convinced that genes retained all the crucial information necessary for organisms' generation, growth, survival and reproduction (Sarkar, 1998).
One of the fundamental discoveries of the 20th century was that DNA was the genetic code's physical structure (Watson & Crick, 1953) and, since then,
many studies have disclosed the complicated pattern of regulation and expression of genes, which involve RNA synthesis and its subsequent translation
into proteins.
Nowadays, if we define genes from a physical/molecular point of view, we usually consider them as a specific sequence of DNA (and its control
region), which is inheritable and codes for a product (Protein or RNA) that has a

Biological Networks And The Biomedical And Genomic Fields
In the past two decades, technological advances in the biomedical and genomic fields have generated enormous volumes of –omics data. These data
continue to be scattered in various databases accessible through the World Wide Web (Table 1), there have been some significant efforts to integrate
these to answer specific questions (e.g., candidate disease gene prioritization1, tissue–specific interaction networks2, etc.). Concomitant with the
development of specialized powerful gene and protein and disease variant annotation databases, there has been an explosion in the number of
publications in the scientific literature. For example, in October 2015, there were approximately 43000 journals in PubMed (ftp://ftp.ncbi.nih.gov
/pubmed/J_Entrez.txt) and more than 21.5 million PubMed abstracts. Collectively, these resources represent different facets and also our current
knowledge of pathophysiological mechanisms. These heterogeneous and humongous data resources have spurred the demand for development of
robust and efficient computational approaches to store, process, integrate, analyze, interpret and generate novel hypotheses.
Biological networks share several features (e.g., scale–freeness and small–world properties) with social and communication networks3. Hence, the
algorithms used for analyzing social networks or Web networks are equally relevant and useful for processing or interpreting biomedical and –omics
networks. The various types of the –omics data, such as protein

Substance Use Disorders Are Chronic And Recurrent. Impulse...
1.6 Guiding principals 1.6.1 Longitudinal data analysis Substance use disorders are chronic and recurrent. Impulse control, which is a predisposition
to and/or a consequence of substance use disorders, is also a core behavioral domain underlying many HIV risk behaviors. Unlike some HIV risk
behaviors such as engaging in unprotected sex, substance use disorders are more proximally associated with brain biology. In order to study HIV risk
behaviors among injection drug users, we will use the data in a longitudinal manner rather than reducing the data to a cross–section or single measure
(e.g., lifetime dependence). The reason is that a longitudinal data provides more valuable information about the long–term trajectories of the HIV risk
behaviors of injection drug users. This information may yield a phenotype that reflects severity and intensity in a way that is more strongly related to
the underlying biology of the trait. Using longitudinal ALIVE injection data, we borrow the concept of "pack–years" to create our phenotype, injection
years, (Caporaso et al., 2009) and analyze the composite HIV risk phenotypes of the trajectories of the participants. (Smith et al., 2015) The lives and
relationships of injection drug users tend toward instability; hence, there exists virtually no perfect attendance record for any single participant in this
study. For this thesis, we accessed the ALIVE cohort, a longitudinal community–based study, and we use statistical approaches to impute the

The Disease Of Common Diseases
Common diseases such as diabetes, cancer, autism, and age–related macular degeneartion effect substantial number of people. Understanding of genetic
causes of these diseases will provide fundamental insight for preventing, diagnosing, and eventually curing these diseases. In the past few decades,
more than a thousand of rare Mendelian diseases causative genes have been identified by combination of linkage analysis with positional cloning (http:/
/omim.org/). However, this strategy does not have enough power as applied to common diseases, in which usually multiple genetic and environmental
risk factors contribute to disease development, and each risk factor only account for a small fraction of the influences (Risch, 2000).
Thereafter, ... Show more content on Helpwriting.net ...
In GWAS, a set of sequence variants are used as genetic markers to discover disease associated regions across the human genome, and subsequently to
detect causative variants within these regions. As relying on the assumption that the disease risk variants will be in linkage disequilibrium (LD) with
one of the marker variants tested, this strategy provides the potential to test any region and gene across the genome for disease association. To apply
GWAS, it is necessary to establish a human genetic variant catalog with characterization of their allele frequencies and LD pattern among different
populations.
The first human genome sequence variation map with 1.42 million SNPs was created by the international SNP Map Working Group in 2000
(Sachidanandam et al., 2001). The SNPs localize either within or close to exons, and the map only described the information on the nearby genes and
other genomic features of the SNPs without characterizing their allele frequencies and LD patterns. It was applied for linkage study, but not enough for
association studies
Until 2002, the international HapMap consortium launched a project with aim to construct the first comprehensive human genetic variant database to
facilitate investigation of the genetic risk factors of human diseases, especially common diseases (2003). The HapMap project consists of three phases
lasting from 2002–2009. The

First Generation Sequencing ( Ngs ) Technologies
Advances in next–generation sequencing (NGS) technologies have offered new and practical approaches for crop breeding; 1) whole–genome
resequencing (WGR), 2) genotyping–by–sequencing (GBS), 3) genome wide association studies (GWAS), and 4) genome editing technologies (GET).
The cost and time for sequencing and genotyping have continuously and dramatically decreased by the developments of diverse high–throughput
platforms. The extensive production and active utilization of genomic resources including genomics tools and resources for crop breeding programs
created a new term, genomics–assisted breeding (GAB) (Varshney et al. 2005). The landscape of soybean breeding programs has been accelerated
along with advance in the genomic era. Advances in NGS technologies have taken the implementation of SNPs for genomic and genetic studies and
NGS has become a turning point for next generation breeding programs due to its reduced sequencing cost (Kim et al. 2016).
Whole–genome resequencing (WGR)
Resequencing of elite cultivars, landraces, and wild genotypes based on the Williams 82 reference genome sequence (Schmutz et al. 2010) has become
an important tool to study allelic variation, domestication events, allele diversification at candidate gene loci (Chung et al. 2014; Kim et al. 2010; Lam
et al. 2011). As a good example of WGR approach for nematode resistance in soybean, Xu et al. (2013) identified two RKN candidate genes in 29.7 kb
interval through the resequencing of 246

Thesis On Psoriasis
Abstract:
Psoriasis is a disease of chronic systemic inflammation that involves not only the skin, but also internal organs. The frequency of Non–alcoholic fatty
liver disease was found to be significantly greater in psoriasis patients with increased risk of atherosclerosis and cardiovascular disease. A large
number of immunes is found in Psoriatic skin and this immune produce chemokine's, cytokine and inflammatory molecules. The exact role of genetics
in psoriasis is still unclear and an overlap between some psoriasis loci and those identified in other autoimmune or inflammatory diseases has been
reported.
Introduction
Psoriasis affects 2–3% of the European population. It is common found less in an individual of Asian descent (0.1% ... Show more content on
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In the Nurses' Health Study II, increased body mass index (BMI) correlated with an increased incident rate of psoriasis, and hip circumference and
waist–to–hip ratio were all associated with a higher risk of incident psoriasis. 37 The psoriasis that are associated with metabolic syndrome and increase
risk of cardiovascular disease are non–alcoholic fatty liver disease (NAFLD) and chronic plague. . NAFLD is the hepatic manifestation of metabolic
syndrome, with its key component being visceral obesity. 38 The prevalence of NAFLD is 10–24% of the general population worldwide, increasing to
57.5–74% in obese individuals. The mortality was increased in patients with NAFLD compared with the general population and in the National Health
and Nutrition Examination Survey (NHANES III) study, the NAFLD cohort had both increased overall mortality and liver–related mortality compared
with individuals without liver disease. 39 While in most patients, NAFLD does not progress beyond simple steatosis, it may progress to
Non–Alcoholic Steato–Hepatitis (NASH). The prevalence of NASH also correlates with obesity, with waist–to–hip ratio and abdominal obesity
reported to be predictors of NASH. Diagnosing patients with NAFLD and identifying those with NASH is challenging, as they are generally
asymptomatic. Clinical presentation and current radiological modalities may not be reliably to

The Evolution Of Eugenics
From evaluating the history that eugenics has imposed, its negative practice has been marked in ways of unrighteous holocaust and genocides
worldwide. The word "eugenics" has been worldly defined and seen as the destruction of undesirable traits, in all reality people. However, the practice
of altering or ridding of specific genes or minority group has changed through the evolution of time. Subcategorizing, eugenics has modernized and has
advanced to the use of prenatal screenings, intentional selective breeding within agriculture, gene therapy, and possible human genetic engineering.
Both articles that will be discussed, centralizes around the idea of genome sequencing. Specifically by focusing on the discovery of specific variant traits
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Covered by the Pan–African array, genotypes for approximately 2,176,716 SNPs were extracted from the 1000 Genomes Project Phase I data to be
used for examination. The selection and observation of these allele frequencies were aimed to find ancestry–informative markers. Calculation of the
Shannon Information Content (SIC), which took mutual information content and found the fundamental limits of each SNP, was obtained with the
CEU and YRI samples. These AIMs then went through another selective process based on linkage disequilibrium (ID) to accept and reject SNPs.
Based on the SIC, the highest ranked SNP was selected as an AIM candidate which concluded to 8 AIM candidates in a 4 cm region. To avoid
overpopulation of markers, SNPs within a 0.25 cm region of the selected candidates were omitted and, by this system it ensured good coverage across
the entire genome. Using the ANCESTRYMAP, the significance, quality and informative value of the AIMs were further analyzed at each SNP to
measure uncertainty in ancestry interference at a specific locus. Detected AIMs were identified later to be conferred with other previously published
samples. This comparison is shown in Figure 1C where the previously published samples were generalized around 0.1–0.12 proportion of variance
explained (PVE) of pc1 ranging past 80

Genetic Identification of Major Psychiatric Disorders Essay
Most major psychiatric disorder diagnoses are defined as descriptive syndromes on the basis of expert consensus. The Diagnostic and Statistical
Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD) are the standard diagnostic tools used by psychiatrists and
clinicians world–wide. Unfortunately, these manuals are classified by clinical agreement and encounter revision every few years. Perpetual revision
and increased medicalization of mental disorders also creates a dilemma for diagnosis and treatment of psychiatric disorders such as autism spectrum
disorder (ASD), schizophrenia, attention deficit hyperactivity disorder (ADHD), major depressive disorder and bipolar disorder. Diagnostic
classification and ... Show more content on Helpwriting.net ...
While French physicians consider ADHD a psychosocial condition rather than a biological, only 0.5% of French children are diagnosed with ADHD.
Conversely, 11% of US children are diagnosed as well as prescribed drugs such as Ritalin and Adderall. The over diagnosis of child–onset ADHD in the
US also correlates with the rise of Ritalin prescription and abuse in school and college age adolescents (Mayes et al., 2008). Although physicians are
working to implement greater scrutiny on false diagnoses of ADHD, there is still heavy misuse among the adolescent population and variability of
doctor bias. The inconsistency in both reliable diagnostic and treatment consensus emphasize the imperative to implement stronger genetics based
studies of psychiatric disorders. Such studies to pinpoint genes, gene products and eventually, neuro–biological pathways related to mental disorders
can elucidate focused diagnostic tests and effective treatments for mental health patients. Population based studies were among the first scientific
studies to confirm the heritable nature of mental disorders. Since the 1970s, psychiatrists clinically observed mental disorders among family members
and hypothesized their possible heritable tendencies.
Such hypotheses could not be empirically proven until researchers began doing twin and family studies. Before the Lichtenstein et al. (2009) family
study, several population–based studies were conducted,

The Importance Of The Human Genome Project
Building off of the work conducted by the Human Genome Project to sequence the entire human genome, the ENCODE Project seeks to delineate the
function of the elements identified within the project. Through the collaboration of many different institutions, scientists, and laboratories, the
ENCODE Project has been able to identify and assign functions to numerous, including previously unstudied, elements within the genome and further
genome–wide understanding beyond just that of protein–coding sequences. Utilizing different biological assays, scientists systematically mapped areas
of transcription, chromatin structure, histone modification, and transcription factor association (ENCODE Project Consortium 2012). ENCODE
focused on... Show more content on Helpwriting.net ...
However, it also illuminated the gaps in understanding that still exist, such as organizational and mechanistic features. The large amount of data
covering numerous cell types from the ENCODE Project creates a resource to be used in the studies of genetic disorders and illnesses and provide
testable hypotheses for experimental analysis. ENCODE focused on a limited number of cell types and factors. Future studies could further
understanding of the genome and potentially fill in the gaps by expanding the number of cell types and factors examined (ENCODE Project
Consortium 2012).
Discussion
The ENCODE Project seeks to determine the functionality of the elements of the human genome. ENCODE has their own definition of functionality,
which includes any discrete genome segment that encodes a defined product or displays a reproducible biochemical signature. With the rapidly
degrading definition of the gene in recent years due to insights from projects like ENCODE and the discovery of pervasive genomic transcription, the
ENCODE definition of functionality could be the key to determining the new definition of a gene. Historically, a gene indicated a piece of DNA which
ultimately had a protein product,

Genetic Variation Between Human Populations
Population demographic factors such as age, sex, diet and ethnicity explain the largest proportion of genetic variation between human populations
(Fumagalli et al., 2011). Infectious agents including viruses, bacteria and protozoa are likely one of the strongest evolutionary drivers of the remaining
genetic diversity within and between populations, as a result of the selective pressure they inflict in regions where infection is endemic. Mortality is
the strongest selective pressure which is imposed by an infectious agent. Any genetic variant associated with an improved response to that pathogen is
likely to be a target for selection (Fumagalli et al., 2011). Positive selection results in the increased frequency of a beneficial allele. Balancing selection
maintains diversity, while negative selection eliminates deleterious variants. This process of natural selection leaves behind distinctive signatures of
selection that can be exploited to identify regions of the genome under selection (Karlsson et al., 2014). Signatures of selection are distinctive because
they reflect uncommon patterns of allele frequencies at a particular locus when compared to the underlying genetic variation. Candidate based gene
approaches, Genome wide association studies (GWAS), haplotype based methods and various statistical tests such as Tajima's D statistic are used to
detect these signatures of selection within the human genome. This essay uses specific examples to discuss the evidence of

Prostate Cancer In Family
Prostate cancer is one of the most common cancers among men, in both Western developed countries and worldwide (Ferlay 2008). It is a cancer that
is only limited to males, as only males have prostate glands. The exact etiology is still unknown; however, it is thought to be a multifactorial disease
with inherited genetics playing a major role (Xu 2013). Particularly, people with fathers and brothers with prostate cancer are at increased risk for
developing it themselves. Other male relatives have also shown a linkage, especially if the relative was diagnosed young (Al Olama AA 2014). This
report discusses how prostate cancer aggregates in family, via the analyses of heritability, twin and adoption studies, family pedigrees, and how specific
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These studies compare allele/genotype frequencies of SNPs between population cases and controls. The low–penetrance genes of prostate cancer found
are the following: Amundadottir and colleagues found a loci at 8q24 (Amundadottir 2006) with the strongest associated SNP as rs1447295 with a
relative risk (RR) for prostate cancer estimated at 1.72. This finding was later corroborated with the results of the first two GWAS of prostate
cancer in May 2007 (Amundadottir 2006 & Gudmundsson 2007). These initial GWAS studies analyzed 550,000 SNPs across the genome in cases
and controls of European origin nested from the Cancer Genetic Markers of Susceptibility (Gudmundsson 2007). Yeager and colleagues confirmed
the prostate cancer association with rs1447295 and identified another independent association at 8q24 (rs6983267). The estimated RRs were 1.26
and 1.58 for heterozygous and homozygous carriers, respectively (Yeager 2007). Gudmundsson and colleagues identified another new prostate
cancer association at 8q24 (rs16901979). The estimated RR was 1.79 (Gudmundsson 2007). Two independent loci at 17q12 and 17q24 were also
found (Gudmundsson 2007). Duggan and colleagues found one locus at 9q33 (Duggan 2007). Thomas and colleagues found four novel loci at 7p15,
10q11, 10q26 and 11q13 (Thomas 2008).

Societal Impacts Of Genetic Study Of Intelligence
SOCIETAL IMPACTS OF GENETIC STUDY OF INTELLIGENCE: Throughout history racism has been centered on phenotypic differences between
races such as skin color. Also, there was a multitude of false information that was created by racism, for example, the claim that certain races have the
predisposition to be less intelligent than others. In 1994, Richard J. Herrnstein and Charles Murray published The Bell Curve: Intelligence and Class
Structure in American Life. This controversial bestseller differences between races and classes were the result of differences in inherited intelligence
which could not be changed. This has caused many people in the scientific community to question if the study of intelligence can remain societally
neutral. Roberts... Show more content on Helpwriting.net ...
These study methods allow researchers to look for similarities and differences within the genome of individuals of different intelligence levels. Using
single nucleotide polymorphism testing, researchers are able to look at single base pairs within the genome and make comparisons within a population.
With the technology that has developed in the last few decades, the study of intelligence has become much more complex and in depth which has
allowed geneticists to see trends that they have not seen before. POLYGENIC: With the new genetic study technologies of the twenty first century,
researchers are able to conduct genome–wide analysis studies as well as single nucleotide polymorphism studies which can be used to determine which
genes, if any, code for intelligence. A study by Benyamin et al. (2014) used single nucleotide polymorphism testing to compare the genomes of 17,989
children. The authors looked for genes in which children of similar intelligence shared many single nucleotide polymorphisms. However, the authors
did not find any single nucleotide polymorphisms that reached a genome–wide significance value. Thus, the authors concluded that this result points to
intelligence being the result of the aggregate effect of many genes within the genome and not just one specific "mother gene". However, while

Research Project : Using Relatedness Analyses
Research Project Description
a.Student Name: Md Manzur Rahman Farazi
b.Faculty mentor: Mehdi Maadooliat Co–Mentor: Steven J. Schrodi, Associate Research Scientist, Center for Human Genetics, Marshfield Clinic
Research Foundation
c.Project title: Using Relatedness Analyses in a Large Kinship to Identify Genes Underlying Rheumatoid Arthritis (RA)
d.Background
Introduction:
Homo sapiens are highly studied organisms by reason of abundant erratic and communal diseases such as obesity, heart disease, diabetes, and others.
Most diseases have solid transmissible components, suggesting a large role of genetic variations in the molecular pathogenesis of diseases.
Genome–wide characterization of the levels and patterns of human genetic variation has enabled geneticists to debrief this variation for association with
complex phenotypes, including common diseases.
SNPs (single nucleotide polymorphism or simple nucleotide polymorphism) are a common type of genetic variation among human being. A SNP is a
variation in a single nucleotide which may occur at some specific position in the genome, where each variation is present to some appreciable degree
(>1%) within a population (Scitable). A SNP may involve the replacement of the nucleotide in a position in theDNA molecule. In the human genome
there are approximately 10 million SNPs, once in every 300 nucleotides. These dissimilarities are found usually in the DNA amongst genes. They act
like biological indicators which help

Genomic Structural Variants
Genomic structural variants (SVs), including deletions, duplications, inversions, and translocations of genetic sequences, account for at least five times
more variable base pairs than single nucleotide variants among human genomes. However, traditional genome–wide scans for adaptive evolution and
disease association tend to ignore thousands of complex structural variants because these scans rely heavily on intact linkage disequilibrium blocks.
This is because a majority of deletion polymorphisms in the human genome is not in linkage with single nucleotide variants around it due to frequent
gene conversion events in this locus. Recent locus–specific studies have investigated a handful of such complex structural variants and have made ...
Aim 1. Resolving the haplotype architecture of GHRd3 to determine its functional and evolutionary impact: In our preliminary studies, we have now
resolved the haplotype architecture using focused analysis of thousands of genomes. This will allow us to thoroughly interrogate associations of
different GHR haplotypes with metabolic and developmental diseases, expression and methylation and levels of neighboring genes in different tissues.
In addition, using population genetics and model–based analysis of the newly resolved haplotypes will enable us to trace back the adaptive pressures
acting on the locus, shedding light on the evolutionary forces maintaining this deletion in the population.
Aim 2. Determining the mechanisms through which GHRd3 affect cell function: Based on previous studies, we hypothesize that GHRd3 leads to
multiple downstream consequences in the growth hormone pathway, including sensitization to growth hormone stimuli. We have now established
CRISPR–Cas9–induced isogenic human cell–lines with all three possible GHRd3 genotypes. Using this experimental model, we will comparatively
measure the impact of growth hormone treatment to rate of cell division and to growth

Genome Wide Association Studies ( Gwas ) Essay
In recent years, genome–wide association studies (GWAS) have successfully tagged thousands of disease– or trait–associated genetic loci. However,
molecular mechanisms linking the locus to the disease phenotype often remain unclear. Moreover, for most complex diseases and traits, associations
found in GWAS explain only a small proportion of the phenotypic variation (129, 130). For example, although 71 independent loci have been
associated with Crohn 's Disease, they account for only 23% of the estimated heritability (131). GWAS of psychiatric diseases show an even less
favorable picture. For instance, schizophrenia has an estimated heritability of 80% (132, 133), but observed genetic variants currently account for less
than 1% of the variance (134). To bridge this gap between genotype and disease phenotype and to better understand the biological mechanisms and
translational possibilities, the genotype–driven approach, aided with deep phenotyping, appears to be a more appealing and powerful strategy (135,
136). A limitation of this approach however, is that the disease pathologies are often tissue– or cell type–specific (137–141), and due to ethical and
practical reasons, deep phenotyping analyses are often only feasible in easily available surrogate tissues such as blood, particularly in large
population–based gene identification studies. The iPSC technologies discussed here in this chapter, along with new sequencing technologies,
genome–wide assays, and comprehensive genome

Letter Of Intent Template Essay
Letter of Intent Template
HSC 4730 Health Science Research
PD/PI Name:
Ja'Terra Robinson
Affiliation/Institution:
Florida State College at Jacksonville
Request for Proposal (RFP) from the National Institute of Health (NIH)–Choose One Pharmacokinetic and Pharmacodynamic Studies for Medications
Development Transmission of Human Immunodeficiency Virus (HIV) In Semen Getting from Genes to Function in Lung Disease. X Developmental
Mechanisms of Human Structural Birth Defects Eunice Kennedy Shriver National Institute of Child Health and Human Development Nanoscience and
Nanotechnology in Biology and Medicine
Place an "X" in the box next to the RFP topic to which the proposed research is most relevant. Mark only one subtopic. ... Show more content on
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There was a broad consensus for five priority areas for future research, to integrate approaches across different technologies and to include diverse
populations for future human studies. There is a need for creating new collaborations with versatile teams that combine bioinformatics, genetics,
molecular biology, and cell physiology.
This is a summary to discuss the direct relevance of the proposed research topic to selected subtopic. You should include the following:
–explain the problem you are trying to solve
–your basic approach to solving the problem
–what solution you expect (if any)
–the impact this will have Getting from genes to function in Lung Disease Recent results from genome wide association studies show that
lung–relevant phenotype have emphasized how powerful the shortcomings are in their approach. Even though new genes and changes have been
identified a large part has still been unidentified. As well as, in the disease development the function and mechanisms of how they develop the disease

is still unknown. The National Heart, Lung, and Blood Institiute assembled a 2 day workshop to address the shortcomings and consider future
directions for lung phenotypes.
В·Background and rationale
The ultimate goal of the workshop was to provide recommendations to the Institiute to fill in the gaps of the knowledge of lung disease genetics by
applying different approaches.The workshop covered

Type 2 Diabetes Analysis
Summary
Background Type 2 diabetes mellitus (T2D) is a complex, heritable, and metabolic disease. And understanding the genetic underpinnings of T2D is a
pivotal topic in complex traits analysis. We aimed to use meta–analysis and multi–omics studies to investigate the genetic architecture of type 2
diabetes.
Methods In this study, 243,218 individuals were included from three cohorts: DIAbetes Genetics Replication And Meta–analysis (DIAGRAM), Genetic
Epidemiology Research on Adult Health and Aging (GERA) and UKBiobank (UKB). METAL was used to perform the meta
–analysis on these three
cohorts. Based on the meta results, we conducted Summary–based–results Mendelian Randomization (SMR) analysis on expression levels. We also
used GCTA methods to... Show more content on Helpwriting.net ...
1. We discovered 2029 SNPs at P < 5 Г—10–8, and after clumping based on GERA genotypes information, there were 48 independent loci significantly
associated with T2D (Supplementary Table 1). The most significant association in this meta–analysis was rs7903146 located at TCF7L2 in
chromosome 10 (P=5.17 Г— 10–142), which was previously reported by many studies(5–9). Out of these 48 loci, we used a more stringent threshold
and 3 loci (MBNL1, C5orf67 and HORMAD2–AS1) were newly identified at P < 1 Г— 10–8. Meta–analysis results of these 3 loci and in each
individual cohort were shown in Table 1. Genome–wide P values of association results across all chromosomes were displayed in Figure 2. To get
more about the loci information and provide fast visualization of meta–analysis results, we plotted locus zoom(10) of three novel loci (Supplementary
Figure

Dihybrid Cross Lab Report
Discussion (1226 words)
From dihybrid test crosses, map distances of 0.69 m.u. between purple and apterous, 5.71 m.u. between black and purple, and 7.56 m.u. between
black and apterous genes were determined. The calculated map distances of 0.69 and 5.71 between more closely linked genes are consistent with
published distances of 0.7 and 6 map units respectively. Inconsistencies between published data and calculated map distances in regards to larger map
distances, such as between black and apterous genes, are due to the nature of dihybrid test crosses. The greater distance between black and apterous
genes increases the likelihood of multiple crossovers. Double crossovers are unaccounted for in dihybrid crosses, thus resulting in RF and map ... Show
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Thus, more accurate RF and map distances are generated from trihybrid crosses. Moreover, double recombinants are useful in determining gene order in
trihybrid crosses. The simultaneous derivation of map distances and gene order from a single cross signify the efficiency of trihybrid crosses.
Limitations of this method of gene mapping decrease accuracy of data (Hartwell et al. 2004). The map generated from dihybrid crosses does not
directly translate to the physical location of genes on a chromosome. While gene order is maintained, map distances may not correlate with distances on
chromosomes. This is because DNA between genes does not always correspond with map units, and due to multiple crossovers which are unaccounted
for in trihybrid crosses. This increases inaccuracy of data, especially between more separated genes. Further, the 50% RF limit leads to less detailed
measurements of distances on chromosomes. As recombination does not occur more than 50% of the time, genes further apart on chromosomes cannot
be accurately mapped. However, a more accurate map can be established through adding smaller distances.
Emerging techniques facilitate genetic mapping in humans (Altshuler et al. 2008). Genome–wide association studies through mapping single
nucleotide polymorphisms (SNPs) are useful in identifying loci associated with disease susceptibility. SNPs are common genetic variations which

Alcohol Dependency Summary
The article by Bierut et al. 2010 is a discovery science article, in which there are no hypotheses tested. This article focuses on alcohol dependence and
the genetic influences that may contribute to the rapid growing dependency. Various case subjects were used to analyze the results from, the
Collaborative Study on the Genetics of Alcoholism (COGA), Family Study of Cocaine Dependence (FSCD) in addition to the Collaborative Genetic
Study of Nicotine Dependence (COGEND). This genome–wide association case study Bierut et. al analyzed various single nucleotide polymorphisms,
likewise known as, SNPs, that are capable of being genetically linked to alcohol dependency. SNPs are nucleotides that contain genetic variation in the
genome as well as, vary between individuals. ... Show more content on Helpwriting.net ...
They correspondingly focused on a gene that known for its linkage to alcohol dependency, GABRA2. GABRA2 functions as a neurotransmitter in the
brain that coincides with the behavior effects of alcohol (Beirut et al., 2010). Using their knowledge of SNPs with the GABRA2 gene, they compared
approximately в‰€1,900 individuals of European and African
–American descent with alcohol dependency issues to в‰€1,900 individuals that have
been exposed to alcohol, nonetheless had no known link to dependency. The results of the case presented that out of studied individuals,
European–American males were the most commonly affected, however of the 15 SNPs that were studied with them, none displayed a correlation that
was higher than the p–value threshold of

Alopecia Areata Research Paper
Alopecia areata (AA) is an autoimmune disease that causes temporary or permanent hair loss. The body attacks its own hair follicles, which ultimately
causes them to stop growing. Typically, it is found in small patches on the scalp but it can be diagnosed anywhere on the body. According to
Petukhova et al. (2011) this disease physically impacts 5.3 billion people just in the United States, affecting about 1–2% of the population. There is no
known cure of AA and there is little evidence suggesting it is stress related. Geneticists have been able to use genome wide association studies (GWAS)
to recognize genes that have affiliation with the onset of alopecia areata. Alkhalifah et al. (2010) observed monozygotic twins because they are likely to
have similar criterions and patterns of hair follicle deterioration. They also observed that AA might be inherited due to patients having a family history
of this autoimmune disease. Human leukocyte antigens genes (HLA) are affiliated in alopecia areata along with several HLA class I and II alleles
(Alkhalifah et al. 2010). The HLA class II antigen is a main contributor to the development of AA. This gene is a big expresser on the hair follicles
and it is expressed on immune cells, giving antigen peptides to a specific T cell, CD4+. These findings suggest that CD4+ cells do indeed ... Show more
content on Helpwriting.net ...
According to Alkhalifah et al. (2010), due to genomic wide association screening there has

The Risk Factors of Osteoarthritis Essay
OA has a complex pathology, with numerous environmental and genetic risk factors. Generally, OA is thought to be caused by a complex
interaction between environmental and genetic factors (Valdes et al., 2009). A variety of epidemiological studies have demonstrated that genetic
susceptibility is a key regulator of OA aetiology (Peach et al., 2005). Genetic variations may influence several OA risk factors, including obesity,
skeletal shape, bone mass and synovitis (Valdes et al., 2011a). Furthermore, it has been shown that generalized OA phenotype, sensitivity to pain and
disease progression may be also determined by genetic susceptibility (Valdes et al., 2010a; van Meurs et al., 2009; Kerkhof et al., 2010).
In the 1940s familial clustering ... Show more content on Helpwriting.net ...
OA is generally recognized as a complex multi–factor disease that has mostly small and modest effect susceptibility loci (Reynard et al., 2012). Over
the past decade efforts have been focused on the search for loci that predispose to OA. The following approaches most often have been attempts to
provide insight into the complexity of OA genetics: genetic linkage studies (LA), genome–wide association studies (GWAS) and candidate gene studies.
LA exploits the fact that genes have a tendency to be inherited together because they are located close to each other. After identification of a linkage,
all genes in the linked region need to be identified and in this manner candidate genes of interest for a disease can be established. LA has been
successful in localizing chromosomal regions containing highly penetrant genetic variants. However, in a common disease, such as OA, the success of
LA is very limited for a number of reasons, including the low power of identification of genes with modest effects and the large impact of
environmental influences (Risch et al., 1996).
After the completion of the Human Genome Sequencing project, which provided the opportunity to systematically search across the genome and to
test large numbers of common genetic variants for association with disease, GWAS have been successfully applied to the study of many complex
diseases. GWAS make it possible to examine the associations of thousands of

Migraine And Coronary Artery Disease Analysis
Migraines rank as the number 7th leading cause of disability worldwide and affects an approximated 14% of the general population. In other words, a
migraine is a headache on steroids. It is a primary headache disorder characterized by recurrent headaches that range anywhere between moderate to
extremely severe. Typically, the symptoms associated with migraines include a pounding sensation in one half of the head, nausea, vomiting, and
sensitivity to light, smell, and sound. Before a migraine comes on, approximately one–third of people experience what is called a migraine aura. A
migraine aura is typically a short period of time accompanied by visual disturbances and can occur with little to no headache. When thinking of a
migraine the first ... Show more content on Helpwriting.net ...
The purpose of this study was to determine the genetic overlap between migraine and Coronary Artery Disease(CAD). The study also aimed to
identify shared genetic risk loci, utilizing a conditional false discovery rate approach and two genome studies of CAD and one for migraine. In
conclusion, the researchers found that the previous findings that CAD and migraine share genetic risk factors. The gene, PHACTR1, showed
significant cross–phenotype association in migraine and CAD. The findings are significant because the results were consistent with present theories
that migraine and Coronary Artery Disease share genetic risk loci and highlight one risk locus in PHACTR1. Researchers can now continue to research
and acquire a better understanding of biological mechanisms and how they may improve our understanding on vascular mechanisms in

##ome-Wide Association Studies : The Human Genome Model...
Genome–Wide Association Studies
Genome–wide association studies (GWAS) are often correlated with personalized medicine. GWAS studies often involve sequencing the entire genome
of patients suffering from a specific disease, to look for shared mutations within their genomes (Bush et al., 2012, p.1). These shared mutations are then
investigated to assure their direct correlation with the disease, in which this mutation can be used to diagnose future patients by identifying the same
mutation in their genome sequence (Bush et al, 2012, p. 3). Occasionally, it is identified that multiple mutations within the genome lead to the same
disease (Bush et al., 2012, p.1). In cases where groups of individuals suffer from specific mutations in disease, ... Show more content on Helpwriting.net
...
9–11). This hypothetical model could be used as a comparison model for the whole genome sequencing of humans: the mutations present in the
sequenced human genome could be directly related to that of the model for a precise identification of the disease present (Cohen et al, 2008, p. 9–11).
The concept of the Human Genome Project has largely affected the conceptualization of the genome model for disease, which would allow
pharmacogenomics to excel in its productivity.
Oncogenomics
Personalized medicine demonstrates a large demand in oncogenomics: the study of the molecular pathways that underlie cancer (Tannock et al, 2016, p.
1289). The gene sequencing of multiple cancers has led to the "progress in molecular pathology [with] decreasing cost, increasing speed and [a] more
comprehensive" evaluation towards treatment methods for specific cancers (Tannock et al, 2016, p. 1289). This process allows for individuals with
cancerous tumours to have the DNA within these cancerous tumours to be screened for their virulence and pathogenicity. Intratumour heterogeneity is
the major setback for the implementation of personalized cancer treatments for tumours: tumours often arise from different tumor cells, which
increases the variability of the target cell for the treatment itself (Tannock et al, 2016, p. 1290). Due to this constant change in the composition of
tumours, a single personalized treatment approach is difficult to come across for full efficacy

What Is The Collaborative Study On The Genetics Of...
Beirut et al. (2010) and Kalsi et al. (2008) focus on genes that are correlated to alcohol dependency or AD. The disease can be described as the
constant need to consume alcohol. Although not as discussed, genetic variants play a role in individuals developing alcoholism. Through a
genome–wide association study, these articles were able to identify and interpret some variants that relate to this disease.
The article by Bierut et al. (2010) is a discovery science article, in which there are no hypotheses tested. This article focuses on alcohol dependence and
the genetic influences that contribute. Various case subjects were used to analyze the results from, the Collaborative Study on the Genetics of
Alcoholism (COGA). In this genome–wide ... Show more content on Helpwriting.net ...
They know that despite displaying a minimal correlation, there is a possibility for various genes to contribute to alcoholism.
The Kalsi et al. (2008) article is a review article, therefore, lacking a hypothesis. The main idea was to identify various genes that are related to
alcoholism and how they affect the brain. The first variant studied was DRD2, a dopamine receptor gene (Kalsi et al., 2008). This gene is known for
being related to addiction and pleasures in life. It is not shocking to know that this gene is elevated in the nervous system, because alcohol raises the
dopamine receptors and causes drinkers to feel as if they need more, thus increasing their happiness. Another gene discussed is the GABAA gene, a
component of the GABRA2 gene. This component when found in AD, spikes an increase in tolerance level, thus creating an effect in the brain to
encourage the individual to continue drinking. Once the tolerance levels have spiked, GABAA and another receptor gene, NPY will induce
withdrawal behavior. These variants, if found at low levels, play a vital role in the onset of alcoholism. While understanding that the NPY gene may
be found in the individuals, the CREB signaling pathway must also be discussed. They observed a study on rodents to drive a correlation between
deficient genes and their correlation to humans. They observed this by analyzing the

Silico Characterization Of The Association Between...
in silico characterisation of the association between rs12670798 and LDL cholesterol Introduction Complex diseases are caused by multiple genetic
and environmental factors working in combination with each other and thus, it is difficult to characterise the contribution of any one factor to the
disease1. However, the widespread adoption of genome–wide association studies (GWAS) has greatly accelerated the rate at which these factors are
discovered and characterised. These studies genotype individuals with different phenotypes (for example, those who are affected or unaffected by a
complex disease) at hundreds of thousands of single nucleotide polymorphisms (SNPs). If a SNP is statistically more common in one phenotypic
group then it is said to be associated with that phenotype2. A GWAS found a significant association between the SNP rs12670798 and low
–density
lipoprotein (LDL) cholesterol3. Previous studies have shown that high levels of LDL cholesterol are associated with increased risk of coronary artery
disease (CAD) 4, 5, a leading cause of morbidity and mortality worldwide6, 7. An increased understanding of the molecular mechanisms which regulate
LDL cholesterol levels will facilitate the discovery and development of novel therapeutics for the treatment of CAD and thus, the investigation of
SNPs which are associated with LDL cholesterol is of upmost importance4. This report details the in silico characterisation of the association between
rs12670798 and LDL

Essay On Genome Sequencing
Description Every state within the United States runs its own newborn screening program which test for at least 30 serious conditions which are
treatable if caught early. The program is designed to save lives and uses the dried blood sample collected during the first week after birth. The blood
sample is used to measure the presence of disease markers. The current newborn screening programs are fast, cost effective, and accurate in
identifying disease before symptoms appear. Genome sequencing cost have now decrease to a price range like other complex medical test to be
readily available for clinical application. It is possible for genome sequencing to replace or supplement the existing traditional panels for newborn
screening tests. The... Show more content on Helpwriting.net ...
The participants will only be enrolled after participating in an informed consent process. The participants have a choice on whether they want to receive
the information or not. The focus of the study is to determine how clinicians and families use the genomic sequence results in their decision making. If
a family wishes not to know their sequence information they do not have to participant. The technological advances in DNA sequencing have made
high throughout sequencing methods faster and cheaper. In contrast this allows researchers to generate larger datasets to be used for genome wide
association studies to identify specific factors associated with human health and disease. Specification The National Institutes of Health in 2008
implemented a genome wide association studies policy to require the data from National Institutes of Health funded studies to share collected data with
the research community to maintain the Genotypes and Phenotypes database. The participants privacy is protected through a controlled access policy
with a requires secondary use of data to be consist with the initial informed consent given. For future usage the research must obtain another consent for
the participants data to be used for future research expand the database. For example, the HeLa Genome Data Use Agreement in August 2013 detailed
the importance of controlling data access to protect research participant privacy. The HeLa

Genotypying Case Study
Genotypying
Single nucleotide polymorphism genotyping was conducted on the Illumina platform by (Song, Hyten, et al., 2013) and genotype data of 52,041
SNPs scored on 14,430 germplasm accessions to develop the Illumina Infinium SoySNP50K BeadChip. SNPs were scored using Genome Studio
Genotyping Module v1.8.4 (Illumina, Inc.) and SNPs with minor allele frequency (MAF) of < 0.05 were ruled out from further analysis. Subsequently
42,041 SNPs with minor allele frequency в‰Ґ 0.05 across 491 genotypes were used for GWAS analysis.
Linkage disequilibrium estimation
Glyma.Wm.82.a2 reference genome will be used to obtain chromosome physical lengths (bp) through SoyBase (Grant, Nelson, et al., 2010) to calculate
genome–wide inter marker distance ... Show more content on Helpwriting.net ...
The STRUCTURE default parameters to be used are an admixture model with independent allele frequencies, a burn–in of 100,000, and an MCMC
replication of 500,000 for K = 1 to 10 subpopulations with five replications. The Wilcoxon signed ranked test implemented in SAS 9.4 (SAS Institute,
2017) is used to select the optimum number of subpopulations (Rosenberg, 2004). The optimum number of subpopulations is the smallest K in the first
nonsignificant Wilcoxon test. Distruct 1.1 (Rosenberg, 2003) is to be used for graphical display of the STRUCTURE output.
Genome Wide Association Mapping
Advances in genotyping technology, reduction in cost of next generation sequencing has led to a rapid increase of molecular markers for genomics
studies (Bradbury, Zhang, et al., 2007, Chaudhary, Patil, et al., 2015). The use of association analysis to study complex traits in plants is now a viable
approach. TASSEL program (Trait Analysis by aSSociations, Evolution and Linkage) (Bradbury, Zhang, et al., 2007) is software used to conduct
association analysis. TASSEL accounts for false positives that arise from population and family structure by structured association (Bradbury, Zhang, et
al., 2007).
For a genome–wide association study the false positive rates of the general linear model (GLM), the mixed linear model (MLM), and the compressed
MLM will be compared to determine the best model to use and subsequently run on TASSEL program (Bradbury, Zhang, et al., 2007).
Hwang,

Bipolar Disorder ( Bd )
Bipolar disorder (BD), or manic depression, is one of the oldest mental illnesses, first being documented in 1st Century Greece by Aretaeus of
Cappadocia. He first noted the link between mania and depression that is so characteristic of the disease. As the years progressed the disease changed
names from "mania" and "melancholia" during Ancient Greece and Rome, to "manico–melancolicus" in the 17th century, "lafolie circulaire" in 1851,
and now, finally, "bipolar" as defined by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) in
1980. Bipolar disorder affects 2.3 million Americans, or 1.2% of the population (Gambaccini, 2012). It is equally represented in men and women and
among all races,... Show more content on Helpwriting.net ...
The first paper, Large–scale genome–wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4, by Sklar et al.,
"combined genome–wide association (GWAS) analysis of 7,481 individuals affected with bipolar disorder and 9,250 control individuals within the
Psychiatric Genomewide Association Study Consortium Bipolar Disorder group (PGC–BD)" (2011). In order to achieve this, they used a variety of
methods including a genome wide association analysis (GWAS), replication study, and a pathway analysis. For the GWAS they used 16,731 BD
samples from multiple overlapping case and control studies facilitated by the Psychiatric Genome–wide Association Study Consortium (PGC) and
47,035 individuals for the replication sample. After receiving the primary genotype and phenotype data for all of the samples, they combined
them into a datasheet with 7,481 unique cases and 9,250 unique controls selected. The sample was broken down with 84% BD type 1, 11% BD
type 2, 4% schizoaffective disorder bipolar type, and 1% other bipolar diagnosis. They used 46,234 SNP's, or single nucleotide polymorphisms, to
directly genotype all 11 groups and 1,016,924 NPs were genotyped for 9 of the groups. SNPs are a single nucleotide that is changed that can result in
a disease by altering a gene's function. They then used a logistic regression of the case statuses on the dosages of SNPs and determined that

Single Nucleotide Polymorphisms Essay
Genome wide association studies (GWAS) have identified many genetic variants that may be associated with genetic disease, most of which lie in
non–coding regulatory elements. As only ~1% of human genes are protein coding, it may hardly be surprising that so many of these implicated features
are found within non–coding regions. The task we must face now is to assess the impact and prevalence of each of these variants which may lead to
breakthroughs in how disease genes are localised and mapped in different individuals and populations.
GWAS is a powerful tool for identifying trends between variants, such as Single Nucleotide Polymorphisms (SNPs), and phenotypes, such as genetic
disease. By analysing the DNA of thousands of people using ... Show more content on Helpwriting.net ...
Detecting patterns of mutually conserved regions may indicate regulatory elements that interact with one another to alter the expression of genomic
regions. These patterns may indicate combinatorial effects, whereby the contribution of multiple elements and their binding sites act as a system to
regulate distant features.
The analysis of populations and gene ancestry, is used to identify wild–type alleles and use these to determine the relative abundance and effect of
variant sequences within mutant alleles, that may confer deleterious effects on the individual. Once we have identified the disadvantageous variants
and the wild–type sequence they have mutated from, we can direct the genome editing tools at our disposal to disrupt these regulatory sequences or
substitute less deleterious bases.
With the information we have gathered from sequencing the human genome and building databases of individuals' genomes, we create libraries of
genes and their products and regulators. Much of the regulation of gene expression discovered has been attributed to non–protein coding genes that may
affect transcriptional machinery–binding or that are transcribed into RNA sequences that regulate the translation of target RNA sequences. The latter is
known as RNA interference (RNAi) and uses smaller, micro RNA sequences, to promote the degradation of target RNA sequences or inhibit their
translation. RNAi actually

Skin Representation Lab Report
The research group carried out a genome wide association to scan for sequence variants that influence hair color, eye color and skin color in the
europeans. Pigmentation in humans is attributed to the number type and cellular distribution of melanosomes. When different number of
melanosomes are produced, they cause the differences in the skin pigmentation. The experiment was done with a sample of people from Iceland and
Holland. The results of this experiment showed how the samples were broadly similar despite the fact that icelanders have more red hair, freckles
and green eyes. They carried out two scans for each eye color, hair color and skin pigmentation traits. There were two overlapping regions on the
MC1R on chromosome 16 and one of them is near a strong candidate for a strong ... Show more content on Helpwriting.net ...
The ultimately summarized the primary and secondary pigmentation traits are associated in the six regions on the genome. The research allowed us to
identify several new variants that account for differences in the pigmentation. Each of these variants are viewed to have a moderate effect on
pigmentation in Europeans. It has been thought that before migrators bought the light skin species out of africa 60,000 years back, our ancestors were
all dark skinned. It is consistent with the correlation of human skin pigmentation and proximity to the equator. The results of this research support the
conclusion that most of the pigmentation variants discovered in this study show positive selection in European populations. The advantage of having a
lighter skin pigmentation is that it facilitates the formation of Vitamin D3 though lighter skin people live in colder areas where there is low exposure
to sunlight/ UV rays. The newly discovered determinants provide promising candidates for for forensic geneticists and for the study of

Cardiovascular Diseases
Several researches investigated the benefits of knowing the genomic sequence and how it is associated with the risk of certain disease. There are
several arguments contrary to genomic research and some are supporting it. For instance The Director of Cancer genetics center at Johns Hopkins
university says "it may become one important determination in patient care, but certainly not the only one" [source]. Several studies doubts that
genomic research providing any extra information about the possibility of getting common diseases, including heart disease and stroke, since such a
disease also involves one's daily routine and lifestyle [res]. On the other side several papers showed the impact that the genomic research can have on
the medical... Show more content on Helpwriting.net ...
The new findings help better understand the cardiac development and effect on clinical care for patients with CHD. In general, cardiovascular disease
(CVD) is a complex disease; no one single gene mutation is responsible for it. Therefore a new genome–wide association study (GWAS) was launched
to investigate a wide range of genes that is associated with the CVD.
Genome–Wide associated Study is a study involving hundreds of thousands of single–nucleotide polymorphisms (SNPs) to be examined in relation to
diseases in hundreds of thousands of subjects. GWAS studies compare theDNA of various subjects having different phenotypes of a specific disease,
to the control subjects in order to identify the genome associated with the disease. Another way to run GWAS studies is by collecting thousands of
hundreds of DNA samples. Using SNPs arrays genetic variants are read, if one variant has a higher frequency in subjects with a specific disease,
which reveals that this genetic variant is linked to the disease.
A GWAS study was done by O'Donnell and his team, revealed 20 new genetic loci related to myocardial infraction and other CVD phenotype
(O'Donnell & Nabel, 2011; Schnabel, Baccarelli, Lin,

Explain the Difference Between Mendelian and Non-Mendelian...
A discussion of the Progress made so far in understanding the Genetic Architecture of Schizophrenia
Schizophrenia: An Elusive Complex Disorder
A discussion of the Progress made so far in understanding the Genetic Architecture of Schizophrenia
Mendelian diseases conform to Mendel's laws of genetic inheritance; segregation and independent assortment. Therefore, every pair of alleles in
diploid organisms, are separated during meiosis and one allele for every trait is passed onto one of the two daughter cells, independently of all other
genes. Thus, depending on the recessive or dominant status of both alleles for a gene, an individual may or may not develop a simple disorder where
one gene is sufficient causality (Mendel, 1865). In ... Show more content on Helpwriting.net ...
R., 2010); * Single genetic locus * Multiple single loci * Additively combining loci
Thus implying either oligogenic or polygenic architecture, with the number of genes and extent of epistasis yet to be clarified (Owen M.J., 2005). To
emulate the observed risk to relatives pattern several variants may be combined in a multiplicative way, as demonstrated by the 'S' curve in figure 2,
where individuals with more than 43 risk alleles will develop the disorder.
Figure 2
Figure 2
Exchange models such as the liability threshold model (LTM), figure 3, can also model Schizophrenia. Both models can be created for many
combinations of allele number, frequency, effect size predicting a steep rise in disease probability for a small percentage of the population. In the LTM
all individuals have unknown liability with both an environmental and genetic component, presentation is sporadic, limited to those that meet the
threshold.
Figure 3
Figure 3
LTM is parameterized solely on the total variance the genetic architecture is accountable for making it a good model to hypothesise upon as it requires
no explicit assumptions for; allele number, frequency and effect size. LTM supports the current range of exchangeable genetic models that have
varying hypothesis but limited statistical differentiation (Wray N. R., 2010). Reduced fecundity in patients decreases genetic variance whilst de novo
mutations exert the opposite force, neither of which can be captured

Integrative Genomic Analysis In Cancer Essay
Other methodologies for integrative genomic analysis in cancer have been studied previously. The review presented in cite{kristensen2014principles}
summarizes a number of different tools and algorithms used in this area. The paper classifies these methods into statistical, machine learning, gene set,
network, and other analysis techniques. Many work has been done to perform an integrated analysis using genetic and gene expression data. In
cite{xiong2012integrating}, the authors illustrated that joint analyses of genomic data increase the power to detect real associations when compared
with gene set methods that use only one genomic data type. They developed a single statistical framework, Gene Set Association Analysis... Show more
content on Helpwriting.net ...
The authors of this paper integrated high–dimensional genetic and proteomic data in a cohort of subjects in which a portion experienced an adverse
event (AE) after primary immunization with Aventis Pasteur smallpox vaccine. They modelled the AE risk using 1442 single nucleotide
polymorphisms as genetic variables and 108 serum cytokine concentrations as proteomic variables. They employed the Random Forests (RF) method to
filter the most important attributes to be used in the building of a final decision tree model. After that, they built a comprehensive model of AE
development by integrating information from previous studies with the genetic and proteomic attributes identified by RF. The biological factors
included in the model support their hypothesized mechanism for the development of AEs involving prolonged stimulation of inflammatory pathways
and an imbalance of normal tissue damage repair pathways.
A novel approach was presented in cite{zhong2010integrating}. This approach uses information from genetics of gene expression studies to investigate
biological pathways enriched for expression–associated genetic loci related with disease in publicly available Genome–wide Association Studies
(GWAS) results. The authors of this paper, first identified SNPs in population–based human cohorts that associate with the expression of genes (eSNPs)
in the metabolically active tissues liver, subcutaneous

Genome Wide Association Studies Essay
Genome wide association study has been very useful in the recent years. It has helped researchers to detect genes that are not detected that easily. With
the detection, it helps the researchers to prevent and treat the particular disease. Breast cancer has been one of the most common cancer in the world
and the most common in women. Even though, breast cancer is detected easily with mammograms or self examination there are times where it can be
hard to detect. Genome wide association studies help to identify the genes that are in risk for breast cancer. Every population has different lifestyle,
genetic variants and other factors. Sometimes not every SNP (single nucleotide polymorphisms) are present in every population. Genome– wide ...
"No studies have investigated the association of the GWAS – identified SNPs with breast cancer risk in Indian population" (Nagrani et al,1). Breast
cancer risk has been increasing in India for the last decade but there haven't been enough studies to identify risk factors related to lifestyle or genetics
(Nagrani et al, 1). The study was conducted at Tata Memorial Hospital, Mumbai, India, to identify lifestyle and genetic risk factors of breast
cancer. This study focuses on examining the risk in SNP loci for breast cancer identified by GWAS in Caucasian and East Asian population
(Nagrani et al, 1). This is one of the first studies to be done on an Indian population to examine a large number of GWAS identified breast caner risk
loci in an adequately powered population based study (Nagrani et al, 1). The cases were aged from 20–69 years with a date of diagnosis not more than
six months. Controls were also aged from 20–69 years of age. The controls were frequency matched to cases by age and region of residence during
enrollment (Nagrani et al, 2). Apart from questionnaire to be filled out, a 10mL blood sample was collected from each study participant in order to
extract genomic DNA (Nagrani et al, 2). "250ng DNA was applied to SNP typing using Illumina's GoldenGate Genotyping Custom SNP Panel assay
(Nagrani et al, 2). The genotyping was completed

An Explanation Of Individualized Medicine
The paper begins with the story of a five–year–old boy, a five–year–old boy who is barely clinging to life. He is so malnourished that he looks half his
age. After a plethora of operations, examinations, and hospitalizations, doctors still had no idea what was wrong with him, that is, until geneticist
Elizabeth Worthey began studying his DNA. Worthey began with the conventional and finished with the unconventional. In order to discover what was
wrong with the boy, Worthey mapped out the genes that determine the protein his cells make. This essentially allowed her to pinpoint the mutation that
was causing the boy's medical problems. This is one of the first examples of "individualized medicine," which uses the genome of the patient to ... Show
more content on Helpwriting.net ...
During the same year as Franklin's discovery, Watson and Crick determined that the chemical rungs that join the two helical strands are made up of
two base pairs. The two base pairs are adenine (A)–thymine (T) or guanine (G)–cytosine (C). They also realized that the order of those two chemical
base pairs that joined the two helical strands "spelled out" the genes and determined the variation of traits in all living organisms. In addition to their
already impressive discovery, they also realized that the two helical strands could be separated for copying, which facilitated the passing on of genetic
information between each generation. A few years following this discovery by Watson and Crick, biochemists Marshall Nirenberg and Har Gobind
Khorana determined the reason for genetic mutations. They occur when the sequence of the chemical bases on the DNA that determine the order of
amino acids that link to create a protein is incorrect. These mutations can cause all sorts of problems, such as diseases. However, sometimes these
mutations are beneficial and allow organisms to better adapt to their environment.
By comparing "good" DNA with "bad" DNA, researchers hope to find out why people with the "bad" DNA are the way they are (why do they have
that disease?), improve methods of diagnosis in order to catch the diseases earlier on, and improve treatment.
However, researchers weren't able to do that until recently. Various discoveries had to happen before

A Study On The Genome Wide Association Mapping Has Become...
Genome–wide association mapping has become a popular way of quantitative trait locus (QTL) identification for the majority of crop plants including
wheat (Triticum aestivum L.). Its advantage over classical bi–parental mapping methods relies on the size of linkage disequilibrium in the mapping
population. The objectives of this study are to determine linkage disequilibrium decay rate and population structure in a winter wheat population of 276
accessions which has been genotyped with the ILLUMINA infinium 90k chip and to identify markers associated with yield and its components,
morphological, phenological, and drought tolerance–related traits.
Wheat is the world's third most important food crop next to maize and rice, (Green et al., 2012). It accounts for one–fifth of total production among
major cereal crops and provides 55 % of the carbohydrates consumed by humans around the world (Bagge et al., 2007). However, wheat
productivity is threatened by both biotic and abiotic stresses and its potential yield is rarely achieved. Crop resistance to both biotic and abiotic
stresses, including drought has been successfully improved by plant breeding through phenotypic selection (Cooper et al., 2009). However, there is a
large yield gap between drought prone areas and ideal production regions for most crops, including wheat. Drought tolerance is a complex quantitative
trait controlled by multiple genes (Mir et al., 2012). It is also complicated by the fact that

Genome Sequencing Of A Plant
Genome sequencing of a plant creates a genomic resource for the plant with the help of which further studies can be conducted on it. But this kind
of a comprehensive resource is only available for a few species. The plants that are recently making their presence felt internationally lack this kind
of a resource despite having numerous health benefits. A valid collection of genome wide screening markers can add to the genomic resource for
such plants. One such crop is Stevia rebaudiana, belonging to the genus Stevia of the sunflower family (Asteraceae), commonly known as Stevia,
Sweet Leaf, Sweet herb of Paraguay, Honey Leaf and Candy Leaf (Madan et al., 2010). Although it is native to Paraguay, it is now successfully being
cultivated throughout the world as an important exotic crop. It is widely grown for its sweet leaves, the source of sweetener products known to contain
4–15% of steviosides which are estimated to be 100–300 times sweeter than sucrose (Mondaca et al. 2012; Ishima and Katayama, 1976; Tanaka, 1982;
Raji Akintunde Abdullateef and Mohamad Osman, 2012). Being a zero calorie sweetener it is finding wide market as it is safer and healthier since
calories can lead to obesity, a risk factor for some chronic diseases such as diabetes mellitus, hypertension, cardiovascular diseases, etc(Savita, Sheela,
Sunanda, Shankar, & Ramakrishna, 2004). Research also shows its effect on decrease in fertility of male rats (Melis 1999) and adult female rats of
proven fertility

Linkage Analysis Essay
As molecular genetic data became available, studies used them to understand human behaviors. Below I briefly summarize the structure of human
genome and introduce the genome–wide association studies (GWAS). In humans, 23 pairs of chromosome constitutes the human genome. For each
chromosome, the nucleotides on the opposite strands connected together to form tens of thousands of base pairs. Normally, the bonds are either
adenine–thymine (A–T) or guanine–cytosine (C–G). These construct the double helix DNA structure. A chunk of a chromosome that relates to certain
functions is a gene. The lengths of genes (i.e., a region of DNA) differ. Mutations of genetic variants in genes can lead to diseases or variations in
phenotypes. Genetic variants ... Show more content on Helpwriting.net ...
Also, the analyzed segments for association studies are at least ten times smaller than the ones used in linkage analysis (10~100 kb vs. 1000 kb).
Therefore, although both association studies and linkage studies use the similar method, by scanning a large scale of the known human genetic
variants, and finding the significant SNPs that relate to the outcomes, association studies have the larger statistical power and are more popular
nowadays. The genome–wide association studies apply the association studies to a large portion of the known common human genetic variants. For
humans, there are about 8 to 10 million common SNPs for whom at least one percent of the population has the minor allele. The minor allele is the
rarely observed genetic variants in the reference population. Mostly, laboratories genotype only about a million of these tag SNPs and impute others.
Both the linkage studies and association studies are hypothesis–free approach which does not require the a priori knowledge of the biological pathways
underlying the study (Belsky and Israel 2014, Manuck and McCaffery 2014). GWAS' features of including many genetic variants and being
hypothesis–free provide researchers with an unbiased and comprehensive method. Only a theoretical assumption is assumed for these association
studies: the common disease–common variant assumption. This holds that multiple SNPs contribute to a single disease

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