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A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies

Single nucleotide polymorphisms (SNPs) are usually the most frequent genomic variants. Directly pedigree-phased multi-SNP haplotypes provide a more accurate view of polymorphic population genomic structure than individual SNPs. The former are, therefore, more useful in genetic correlation with subje...

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Autores principales: Vadva, Zareen, Larsen, Charles E., Propp, Bennett E., Trautwein, Michael R., Alford, Dennis R., Alper, Chester A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721696/
https://www.ncbi.nlm.nih.gov/pubmed/31387299
http://dx.doi.org/10.3390/cells8080835
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author Vadva, Zareen
Larsen, Charles E.
Propp, Bennett E.
Trautwein, Michael R.
Alford, Dennis R.
Alper, Chester A.
author_facet Vadva, Zareen
Larsen, Charles E.
Propp, Bennett E.
Trautwein, Michael R.
Alford, Dennis R.
Alper, Chester A.
author_sort Vadva, Zareen
collection PubMed
description Single nucleotide polymorphisms (SNPs) are usually the most frequent genomic variants. Directly pedigree-phased multi-SNP haplotypes provide a more accurate view of polymorphic population genomic structure than individual SNPs. The former are, therefore, more useful in genetic correlation with subject phenotype. We describe a new pedigree-based methodology for generating non-ambiguous SNP haplotypes for genetic study. SNP data for haplotype analysis were extracted from a larger Type 1 Diabetes Genetics Consortium SNP dataset based on minor allele frequency variation and redundancy, coverage rate (the frequency of phased haplotypes in which each SNP is defined) and genomic location. Redundant SNPs were eliminated, overall haplotype polymorphism was optimized and the number of undefined haplotypes was minimized. These edited SNP haplotypes from a region containing HLA-DRB1 (DR) and HLA-DQB1 (DQ) both correlated well with HLA-typed DR,DQ haplotypes and differentiated HLA-DR,DQ fragments shared by three pairs of previously identified megabase-length conserved extended haplotypes. In a pedigree-based genetic association assay for type 1 diabetes, edited SNP haplotypes and HLA-typed HLA-DR,DQ haplotypes from the same families generated essentially identical qualitative and quantitative results. Therefore, this edited SNP haplotype method is useful for both genomic polymorphic architecture and genetic association evaluation using SNP markers with diverse minor allele frequencies.
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spelling pubmed-67216962019-09-10 A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies Vadva, Zareen Larsen, Charles E. Propp, Bennett E. Trautwein, Michael R. Alford, Dennis R. Alper, Chester A. Cells Article Single nucleotide polymorphisms (SNPs) are usually the most frequent genomic variants. Directly pedigree-phased multi-SNP haplotypes provide a more accurate view of polymorphic population genomic structure than individual SNPs. The former are, therefore, more useful in genetic correlation with subject phenotype. We describe a new pedigree-based methodology for generating non-ambiguous SNP haplotypes for genetic study. SNP data for haplotype analysis were extracted from a larger Type 1 Diabetes Genetics Consortium SNP dataset based on minor allele frequency variation and redundancy, coverage rate (the frequency of phased haplotypes in which each SNP is defined) and genomic location. Redundant SNPs were eliminated, overall haplotype polymorphism was optimized and the number of undefined haplotypes was minimized. These edited SNP haplotypes from a region containing HLA-DRB1 (DR) and HLA-DQB1 (DQ) both correlated well with HLA-typed DR,DQ haplotypes and differentiated HLA-DR,DQ fragments shared by three pairs of previously identified megabase-length conserved extended haplotypes. In a pedigree-based genetic association assay for type 1 diabetes, edited SNP haplotypes and HLA-typed HLA-DR,DQ haplotypes from the same families generated essentially identical qualitative and quantitative results. Therefore, this edited SNP haplotype method is useful for both genomic polymorphic architecture and genetic association evaluation using SNP markers with diverse minor allele frequencies. MDPI 2019-08-05 /pmc/articles/PMC6721696/ /pubmed/31387299 http://dx.doi.org/10.3390/cells8080835 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vadva, Zareen
Larsen, Charles E.
Propp, Bennett E.
Trautwein, Michael R.
Alford, Dennis R.
Alper, Chester A.
A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies
title A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies
title_full A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies
title_fullStr A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies
title_full_unstemmed A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies
title_short A New Pedigree-Based SNP Haplotype Method for Genomic Polymorphism and Genetic Studies
title_sort new pedigree-based snp haplotype method for genomic polymorphism and genetic studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721696/
https://www.ncbi.nlm.nih.gov/pubmed/31387299
http://dx.doi.org/10.3390/cells8080835
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