The genomic basis of medicine

2020 ◽  
pp. 218-235
Author(s):  
Paweł Stankiewicz ◽  
James R. Lupski
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Complex Traits ◽  
Copy Number ◽  
Clinical Medicine ◽  
Association Studies ◽  
Copy Number Variants ◽  
Nucleotide Polymorphisms ◽  
Structural Variations ◽  
Single Nucleotide ◽  
Practical Applications

The first phase of the studies on genetic variation in humans has been focused on single nucleotide polymorphisms and common variation. The large number of single nucleotide polymorphisms identified has enabled successful genome-wide association studies for disease susceptibility risk of complex traits (e.g. diabetes and cancer), but for the most part has had limited practical applications in clinical medicine. This chapter examines the recent technological developments which have enabled a higher-resolution analysis of the human genome and its extensive submicroscopic structural variation, including copy-number variants. Copy-number variants involving dosage-sensitive genes result in several diseases and contribute to human diversity and evolution. An emerging group of genetic diseases have been described that result from DNA rearrangements (e.g. copy-number variants and other structural variations including copy-number neutral inversions and translocations), rather than from single nucleotide changes.

scholarly journals Exome resequencing and GWAS for growth, ecophysiology, and chemical and metabolomic composition of wood of Populus trichocarpa

2019 ◽  
Author(s):  
Fernando P. Guerra ◽  
Haktan Suren ◽  
Jason Holliday ◽  
James H. Richards ◽  
Oliver Fiehn ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Biomass Production ◽  
Complex Traits ◽  
Association Studies ◽  
Populus Trichocarpa ◽  
Exome Capture ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Improvement Programs

Abstract Background: Populus trichocarpa is an important forest tree species for the generation of lignocellulosic ethanol. Understanding the genomic basis of biomass production and chemical composition of wood is fundamental in supporting genetic improvement programs. Considerable variation has been observed in this species for complex traits related to growth, phenology, ecophysiology and wood chemistry. Those traits are influenced by both polygenic control and environmental effects, and their genome architecture and regulation are only partially understood. Genome wide association studies (GWAS) represent an approach to advance that aim using thousands of single nucleotide polymorphisms (SNPs). Genotyping using exome capture methodologies represent an efficient approach to perform GWAS. Results: A GWAS using 461 P. trichocarpa clones, representing 101 provenances collected from Oregon and Washington, and 813K single nucleotide polymorphisms (SNPs), identified a variable number of significant SNPs in association with the assessed traits. Associated single-markers (q< 0.1) ranged from 3 to 110 per trait. The SNPs had a cumulative effect of up to 40.6% of the phenotypic variation of any given trait. Similarly, multiple-marker analyses detected between 16 and 291 significant windows for the phenotypes. The SNPs resided within genes that encode proteins belonging to different functional classes as well as in intergenic regions. Conclusion: SNP-markers within and proximal to genes associated with traits of importance for biomass production were detected. They contribute to characterize the genomic architecture of P. trichocarpa biomass required to support the development and application of marker breeding technologies.

scholarly journals Genome wide analysis reveals single nucleotide polymorphisms associated with fatness and putative novel copy number variants in three pig breeds

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 784 ◽  
Author(s):  
Katie E Fowler ◽  
Ricardo Pong-Wong ◽  
Julien Bauer ◽  
Emily J Clemente ◽  
Christopher P Reitter ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Copy Number ◽  
Copy Number Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide Analysis ◽  
Pig Breeds ◽  
Genome Wide

scholarly journals Copy number variant syndromes are frequent in schizophrenia: progressing towards a CNV-schizophrenia model

2019 ◽  
Author(s):  
Venuja Sriretnakumar ◽  
Clement C. Zai ◽  
Syed Wasim ◽  
Brianna Barsanti-Innes ◽  
James L. Kennedy ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Patient Population ◽  
Copy Number ◽  
Copy Number Variants ◽  
Copy Number Variant ◽  
Effect Sizes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Immune Pathway

ABSTRACTThe genetic underpinnings of schizophrenia (SCZ) remain unclear. SCZ genetic studies thus far have only identified numerous single nucleotide polymorphisms with small effect sizes and a handful of copy number variants (CNVs). This study investigates the prevalence of well-characterized CNV syndromes and candidate CNVs within a cohort of 348 SCZ patients, and explores correlations to their phenotypic findings. There was an enrichment of syndromic CNVs in the cohort, as well as brain-related and immune pathway genes within the detected CNVs. SCZ patients with brain-related CNVs had increased CNV burden, neurodevelopmental features, and types of hallucinations. Based on these results, we propose a CNV-SCZ model wherein specific phenotypic profiles should be prioritized for CNV screening within the SCZ patient population.

scholarly journals Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture

2016 ◽  
Vol 283 (1835) ◽  
pp. 20160569 ◽  
Author(s):  
M. E. Goddard ◽  
K. E. Kemper ◽  
I. M. MacLeod ◽  
A. J. Chamberlain ◽  
B. J. Hayes
Keyword(s):  
Complex Traits ◽  
Genetic Architecture ◽  
Quantitative Traits ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Crop Breeding ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Phenotype Identification

Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement.

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