Cargando…
Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome
BACKGROUND: X-chromosomal loci present different inheritance patterns compared to autosomal loci and must be modeled accordingly. Sexual chromosomes are not systematically considered in whole-genome relationship matrices although rules based on genealogical or marker information have been derived. L...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441635/ https://www.ncbi.nlm.nih.gov/pubmed/32819272 http://dx.doi.org/10.1186/s12711-020-00570-6 |
_version_ | 1783573330832392192 |
---|---|
author | Druet, Tom Legarra, Andres |
author_facet | Druet, Tom Legarra, Andres |
author_sort | Druet, Tom |
collection | PubMed |
description | BACKGROUND: X-chromosomal loci present different inheritance patterns compared to autosomal loci and must be modeled accordingly. Sexual chromosomes are not systematically considered in whole-genome relationship matrices although rules based on genealogical or marker information have been derived. Loci on the X-chromosome could have a significant contribution to the additive genetic variance, in particular for some traits such as those related to reproduction. Thus, accounting for the X-chromosome relationship matrix might be informative to better understand the architecture of complex traits (e.g., by estimating the variance associated to this chromosome) and to improve their genomic prediction. For such applications, previous studies have shown the benefits of combining information from genotyped and ungenotyped individuals. RESULTS: In this paper, we start by presenting rules to compute a genomic relationship matrix (GRM) for the X-chromosome (G(X)) without making any assumption on dosage compensation, and based on coding of gene content with 0/1 for males and 0/1/2 for females. This coding adjusts naturally to previously derived pedigree-based relationships (S) for the X-chromosome. When needed, we propose to accommodate and estimate dosage compensation and genetic heterogeneity across sexes via multiple trait models. Using a Holstein dairy cattle dataset, including males and females, we then empirically illustrate that realized relationships (G(X)) matches expectations (S). However, G(X) presents high deviations from S. G(X) has also a lower dimensionality compared to the autosomal GRM. In particular, individuals are frequently identical along the entire chromosome. Finally, we confirm that the heritability of gene content for markers on the X-chromosome that are estimated by using S is 1, further demonstrating that S and G(X) can be combined. For the pseudo-autosomal region, we demonstrate that the expected relationships vary according to position because of the sex-gradient. We end by presenting the rules to construct the 'H matrix’ by combining both relationship matrices. CONCLUSIONS: This work shows theoretically and empirically that a pedigree-based relationship matrix built with rules specifically developed for the X-chromosome (S) matches the realized GRM for the X-chromosome. Therefore, applications that combine expected relationships and genotypes for markers on the X-chromosome should use S and G(X). |
format | Online Article Text |
id | pubmed-7441635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-74416352020-08-24 Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome Druet, Tom Legarra, Andres Genet Sel Evol Research Article BACKGROUND: X-chromosomal loci present different inheritance patterns compared to autosomal loci and must be modeled accordingly. Sexual chromosomes are not systematically considered in whole-genome relationship matrices although rules based on genealogical or marker information have been derived. Loci on the X-chromosome could have a significant contribution to the additive genetic variance, in particular for some traits such as those related to reproduction. Thus, accounting for the X-chromosome relationship matrix might be informative to better understand the architecture of complex traits (e.g., by estimating the variance associated to this chromosome) and to improve their genomic prediction. For such applications, previous studies have shown the benefits of combining information from genotyped and ungenotyped individuals. RESULTS: In this paper, we start by presenting rules to compute a genomic relationship matrix (GRM) for the X-chromosome (G(X)) without making any assumption on dosage compensation, and based on coding of gene content with 0/1 for males and 0/1/2 for females. This coding adjusts naturally to previously derived pedigree-based relationships (S) for the X-chromosome. When needed, we propose to accommodate and estimate dosage compensation and genetic heterogeneity across sexes via multiple trait models. Using a Holstein dairy cattle dataset, including males and females, we then empirically illustrate that realized relationships (G(X)) matches expectations (S). However, G(X) presents high deviations from S. G(X) has also a lower dimensionality compared to the autosomal GRM. In particular, individuals are frequently identical along the entire chromosome. Finally, we confirm that the heritability of gene content for markers on the X-chromosome that are estimated by using S is 1, further demonstrating that S and G(X) can be combined. For the pseudo-autosomal region, we demonstrate that the expected relationships vary according to position because of the sex-gradient. We end by presenting the rules to construct the 'H matrix’ by combining both relationship matrices. CONCLUSIONS: This work shows theoretically and empirically that a pedigree-based relationship matrix built with rules specifically developed for the X-chromosome (S) matches the realized GRM for the X-chromosome. Therefore, applications that combine expected relationships and genotypes for markers on the X-chromosome should use S and G(X). BioMed Central 2020-08-20 /pmc/articles/PMC7441635/ /pubmed/32819272 http://dx.doi.org/10.1186/s12711-020-00570-6 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Druet, Tom Legarra, Andres Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome |
title | Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome |
title_full | Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome |
title_fullStr | Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome |
title_full_unstemmed | Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome |
title_short | Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome |
title_sort | theoretical and empirical comparisons of expected and realized relationships for the x-chromosome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441635/ https://www.ncbi.nlm.nih.gov/pubmed/32819272 http://dx.doi.org/10.1186/s12711-020-00570-6 |
work_keys_str_mv | AT druettom theoreticalandempiricalcomparisonsofexpectedandrealizedrelationshipsforthexchromosome AT legarraandres theoreticalandempiricalcomparisonsofexpectedandrealizedrelationshipsforthexchromosome |