Rare and population-specific functional variation across pig lines.
Rare and population-specific functional variation across pig lines.
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DOI：
10.1186/s12711-022-00732-8
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发表时间：
2022-06-03
影响因子：
4.1
通讯作者：
Johnsson, Martin
中科院分区：
文献类型：
--
作者：
Ros-Freixedes, Roger;Valente, Bruno D.;Chen, Ching-Yi;Herring, William O.;Gorjanc, Gregor;Hickey, John M.;Johnsson, Martin
预计功能，主要是错义和功能丧失（LOF），和监管的变种是负责品种和经历了不同的选择历史的牲畜物种的遗传系之间的大多数表型差异。然而，关于商业牲畜种群中现有的错义和LOF变异的知识仍然有限，特别是关于种群特异性变异以及它如何影响跨品种基因组预测等应用。我们对来自9个商业猪系的7848个个体的全基因组进行了重新测序（平均测序覆盖率：4.1×），并对440，610个家系相关个体的全基因组基因型进行了估算。根据预测的功能注释（从LOF到基因间）和流行水平（变异分离的品系数量;从私有到广泛）对所调用的变异进行分类。每个类别中的变异进行了检查，其分布沿着基因组，替代等位基因频率，每个网站赖特的固定指数（FST），个人负荷，并与生产性状。在4600万个被调用的变体中，28%是私人的（仅在一条线路中调用），21%是广泛的（在所有九条线路中调用）。具有低重组率的基因组区域富含私有变体。低流行率变异（仅在一个或几个品系中被称为）富集了较低的等位基因频率、较低的FST以及puperoid功能和调节作用（包括LOF和有害的错义变异）。平均而言，与具有其他预测后果的等位基因相比，个体携带的私人有害错义等位基因比预期的要少。只有一小部分的低流行率变异体具有中等等位基因频率，并解释了生产性状的小部分表型方差（高达3.2%）。显著的低患病率变异比非显著变异具有更高的每个位点的FST。这些相关的低患病率变体被高度连锁不平衡中其他更广泛的变体（包括基因间变体）标记。大多数低流行率变异具有低的次要等位基因频率，并且只有一小部分低流行率变异对生产性状的表型方差贡献了可检测的分数。因此，考虑到低流行率变异不太可能明显有利于跨品种分析，例如使用不同遗传背景的参考群体预测群体中的基因组育种值。 在线版本包含补充材料，可通过10.1186/s12711-022-00732-8获取。
It is expected that functional, mainly missense and loss-of-function (LOF), and regulatory variants are responsible for most phenotypic differences between breeds and genetic lines of livestock species that have undergone diverse selection histories. However, there is still limited knowledge about the existing missense and LOF variation in commercial livestock populations, in particular regarding population-specific variation and how it can affect applications such as across-breed genomic prediction. We re-sequenced the whole genome of 7848 individuals from nine commercial pig lines (average sequencing coverage: 4.1×) and imputed whole-genome genotypes for 440,610 pedigree-related individuals. The called variants were categorized according to predicted functional annotation (from LOF to intergenic) and prevalence level (number of lines in which the variant segregated; from private to widespread). Variants in each category were examined in terms of their distribution along the genome, alternative allele frequency, per-site Wright’s fixation index (FST), individual load, and association to production traits. Of the 46 million called variants, 28% were private (called in only one line) and 21% were widespread (called in all nine lines). Genomic regions with a low recombination rate were enriched with private variants. Low-prevalence variants (called in one or a few lines only) were enriched for lower allele frequencies, lower FST, and putatively functional and regulatory roles (including LOF and deleterious missense variants). On average, individuals carried fewer private deleterious missense alleles than expected compared to alleles with other predicted consequences. Only a small subset of the low-prevalence variants had intermediate allele frequencies and explained small fractions of phenotypic variance (up to 3.2%) of production traits. The significant low-prevalence variants had higher per-site FST than the non-significant ones. These associated low-prevalence variants were tagged by other more widespread variants in high linkage disequilibrium, including intergenic variants. Most low-prevalence variants have low minor allele frequencies and only a small subset of low-prevalence variants contributed detectable fractions of phenotypic variance of production traits. Accounting for low-prevalence variants is therefore unlikely to noticeably benefit across-breed analyses, such as the prediction of genomic breeding values in a population using reference populations of a different genetic background. The online version contains supplementary material available at 10.1186/s12711-022-00732-8.
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DOI：
10.1186/s12711-017-0322-5
发表时间：
2017-05-18
期刊：
Genetics, selection, evolution : GSE
影响因子：
--
作者：
Gonen S;Ros-Freixedes R;Battagin M;Gorjanc G;Hickey JM
通讯作者：
Hickey JM
DOI：
10.1186/1297-9686-43-12
发表时间：
2011-03-10
期刊：
Genetics, selection, evolution : GSE
影响因子：
--
作者：
Hickey JM;Kinghorn BP;Tier B;Wilson JF;Dunstan N;van der Werf JH
通讯作者：
van der Werf JH
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
3.3
作者：
Joseph, SB;Hall, DW
通讯作者：
Hall, DW
DOI：
10.1073/pnas.0308518100
发表时间：
2004-02-24
影响因子：
11.1
作者：
Grisart, B;Farnir, F;Georges, M
通讯作者：
Georges, M