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Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits
We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV),...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775389/ https://www.ncbi.nlm.nih.gov/pubmed/24058921 http://dx.doi.org/10.1002/mgg3.16 |
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author | Hinckley, Jesse D Abbott, Diana Burns, Trudy L Heiman, Meadow Shapiro, Amy D Wang, Kai Di Paola, Jorge |
author_facet | Hinckley, Jesse D Abbott, Diana Burns, Trudy L Heiman, Meadow Shapiro, Amy D Wang, Kai Di Paola, Jorge |
author_sort | Hinckley, Jesse D |
collection | PubMed |
description | We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), and white blood cell count (WBC) using SOLAR. Age and gender were found to be significant covariates in many CBC traits. We obtained significant heritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC. We report four candidate loci with Logarithm of the odds (LOD) scores above 2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We also report eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariate linkage analysis of MCV and MCH on chromosome 20 resulted in a higher maximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22, 6q25, and 20q13 are concomitant with previously reported QTL. All other linkage signals reported herein represent novel evidence of candidate QTL. Interestingly rs1800562, the most common causal variant of hereditary hemochromatosis in HFE (6p22) was associated with MCH and MCHC in this family. Linkage studies like the one presented here will allow investigators to focus the search for rare variants amidst the noise encountered in the large amounts of data generated by whole-genome sequencing. |
format | Online Article Text |
id | pubmed-3775389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-37753892014-02-04 Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits Hinckley, Jesse D Abbott, Diana Burns, Trudy L Heiman, Meadow Shapiro, Amy D Wang, Kai Di Paola, Jorge Mol Genet Genomic Med Original Articles We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), and white blood cell count (WBC) using SOLAR. Age and gender were found to be significant covariates in many CBC traits. We obtained significant heritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC. We report four candidate loci with Logarithm of the odds (LOD) scores above 2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We also report eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariate linkage analysis of MCV and MCH on chromosome 20 resulted in a higher maximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22, 6q25, and 20q13 are concomitant with previously reported QTL. All other linkage signals reported herein represent novel evidence of candidate QTL. Interestingly rs1800562, the most common causal variant of hereditary hemochromatosis in HFE (6p22) was associated with MCH and MCHC in this family. Linkage studies like the one presented here will allow investigators to focus the search for rare variants amidst the noise encountered in the large amounts of data generated by whole-genome sequencing. Blackwell Publishing Ltd 2013-09 2013-05-31 /pmc/articles/PMC3775389/ /pubmed/24058921 http://dx.doi.org/10.1002/mgg3.16 Text en © 2013 The Author. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Original Articles Hinckley, Jesse D Abbott, Diana Burns, Trudy L Heiman, Meadow Shapiro, Amy D Wang, Kai Di Paola, Jorge Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits |
title | Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits |
title_full | Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits |
title_fullStr | Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits |
title_full_unstemmed | Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits |
title_short | Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits |
title_sort | quantitative trait locus linkage analysis in a large amish pedigree identifies novel candidate loci for erythrocyte traits |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775389/ https://www.ncbi.nlm.nih.gov/pubmed/24058921 http://dx.doi.org/10.1002/mgg3.16 |
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