The individual and global impact of copy-number variants on complex human traits

The American Journal of Human Genetics, Journal Year: 2022, Volume and Issue: 109(4), P. 647 - 668

Published: March 2, 2022

The impact of copy-number variations (CNVs) on complex human traits remains understudied. We called CNVs in 331,522 UK Biobank participants and performed genome-wide association studies (GWASs) between the copy number CNV-proxy probes 57 continuous traits, revealing 131 signals spanning 47 phenotypes. Our analysis recapitulated well-known associations (e.g., 1q21 height), revealed pleiotropy recurrent 26 16 for 16p11.2-BP4-BP5 22q11.21, respectively), suggested gene functionalities MARF1 female reproduction). Forty-eight CNV (38%) overlapped with single-nucleotide polymorphism (SNP)-GWASs same trait. For instance, deletion PDZK1, which encodes a urate transporter scaffold protein, decreased serum levels, while RHD, Rhesus blood group D antigen, associated hematological traits. Other Mendelian disorder regions, suggesting variable expressivity broad these loci, as illustrated by mapping to Rotor syndrome (SLCO1B1/3), renal cysts diabetes (HNF1B), or Charcot-Marie-Tooth (PMP22) loci. Total burden negatively impacted 35 leading increased adiposity, liver/kidney damage, intelligence physical capacity. Thirty remained after correcting CNV-GWAS signals, pointing polygenic architecture. correlated socio-economic indicators, parental lifespan, age (survivorship proxy), contribution longevity. Together, our results showcase how studying can expand biological insights, emphasizing critical role this mutational class shaping arguing favor continuum diseases.

Language: Английский

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On the concepts and measures of diversity in the genomics era

Current Plant Biology, Journal Year: 2023, Volume and Issue: 33, P. 100278 - 100278

Published: Jan. 1, 2023

Diversity serves as the foundation for breeding and evolution. In science of genomics, investigation genetic variation has long been a prominent subject. Researchers now have access to previously unheard volumes data, thanks development new genomic technologies which allow them thoroughly examine complexity variation. As result, definitions measurements diversity created, taking into consideration things like how is distributed throughout populations, impact natural selection, connection between phenotypic diversity. One crucial idea "genetic ancestry" describes percentage person's composition that may be linked particular ancestral populations. Heterozygosity, measures degree within population, another indicator Recent developments in genomics resulted creation tools methodologies examining addition these conventional measurements. Generally, area research rapidly changing age, with theories being created on regular basis. The origins effects are expected continue revealed our knowledge deepens, substantial ramifications human health, evolutionary biology, variety other domains.

Language: Английский

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Deciphering genomic basis of unique adaptation of Ladakhi cattle to Trans-Himalayan high-altitude region of Leh-Ladakh in India

Gene, Journal Year: 2025, Volume and Issue: unknown, P. 149251 - 149251

Published: Jan. 1, 2025

Language: Английский

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Genome-wide discovery of underlying genetic factors associated with fresh and frozen-thawed semen traits in composite ram breeds exhibiting different cryotolerance

Cryobiology, Journal Year: 2025, Volume and Issue: 118, P. 105197 - 105197

Published: Jan. 18, 2025

Language: Английский

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Runs of homozygosity reveal past bottlenecks and contemporary inbreeding across diverging populations of an island‐colonizing bird

Molecular Ecology, Journal Year: 2023, Volume and Issue: 32(8), P. 1972 - 1989

Published: Jan. 27, 2023

Genomes retain evidence of the demographic history and evolutionary forces that have shaped populations drive speciation. Across island systems, contemporary patterns genetic diversity reflect population demography, including colonization events, bottlenecks, gene flow drift. Here, we investigate genome-wide distribution runs homozygosity (ROH) using whole-genome resequencing individuals (>22× coverage) from six across three archipelagos Berthelot's pipit (Anthus berthelotii)-a passerine has recently undergone We show most dramatic reduction in occurs between mainland sister species (the tawny pipit) is lowest experienced sequential bottlenecks (i.e., Madeiran Selvagens populations). Pairwise Markovian coalescent (PSMC) analyses estimated diverged its ~2 million years ago, with archipelago founded 50,000 colonized 8000 ago. identify many long ROH (>1 Mb) these populations. Population expansion within last 100 may eroded archipelago, resulting a prevalence short (<1 Mb). However, extensive detected suggest strong recent inbreeding bottleneck effects, as much 38% autosomes consisting >250 kb. These findings highlight importance history, well selection drift, shaping genomic diverging

Language: Английский

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Genomic inbreeding analysis reveals resilience and genetic diversity in Indian yak populations

Gene, Journal Year: 2024, Volume and Issue: 928, P. 148787 - 148787

Published: July 23, 2024

Language: Английский

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Genome-wide selection signatures detection in Shanghai Holstein cattle population identified genes related to adaption, health and reproduction traits

BMC Genomics, Journal Year: 2021, Volume and Issue: 22(1)

Published: Oct. 15, 2021

Over several decades, a wide range of natural and artificial selection events in response to subtropical environments, intensive pasture feedlot systems have greatly changed the customary behaviour, appearance, important economic traits Shanghai Holstein cattle. In particular, longevity cattle population is generally short, approximately 2nd 3rd lactation. this study, two complementary approaches, integrated haplotype score (iHS) runs homozygosity (ROH), were applied for detection signatures within genome using genotyping by genome-reduced sequence data from 1092 cows.In total, 101 significant iHS genomic regions containing encompassing total 256 candidate genes detected. There 27 |iHS| with mean > 2. The average number ROH per individual was 42.15 ± 25.47, an size 2.95 Mb. length 78 % detected 1-2 MB 2-4 MB, 99 shorter than 8 A 168 18 islands (top 1 %) across 16 autosomes, which each SNP showed percentage occurrence 30 %. 160 167 associated 52 health-related QTL intervals 59 reproduction-related intervals, respectively. Annotation harbouring clustered signals revealed panel interesting adaptation traits, such as IL22RA1, CALHM3, ITGA9, NDUFB3, RGS3, SOD2, SNRPA1, ST3GAL4, ALAD, EXOSC10, MASP2. further step, 1472 SNPs matched 352 cis-eQTLs 21 tissues trans-eQTLs 6 tissues. For located ROH, 108 13 4 found SNPs. Eighty-one eGenes significantly expressed at least one tissue relevant trait (P value < 0.05) iHS. 47 gene-tissue pairs 37 traits.We provide comprehensive overview genomes combining ROH. Our study provides list immunity, reproduction adaptation. functional annotation, cGTEx resource used interpret SNP-trait associations. results may facilitate identification can help us better understand biological processes mechanisms affected strong ongoing or livestock populations.

Language: Английский

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Runs of homozygosity analysis of South African sheep breeds from various production systems investigated using OvineSNP50k data

BMC Genomics, Journal Year: 2021, Volume and Issue: 22(1)

Published: Jan. 6, 2021

Abstract Background Population history, production system and within-breed selection pressure impacts the genome architecture resulting in reduced genetic diversity increased frequency of runs homozygosity islands. This study tested hypothesis that systems geared towards specific traits importance or natural artificial pressures influenced occurrence distribution (ROH) South African sheep population. The Illumina OvineSNP50 BeadChip was used to genotype 400 belonging 13 breeds from Africa representing mutton, pelt mutton wool dual-purpose breeds, including indigenous non-descript are reared by smallholder farmers. To get more insight into autozygosity ROH islands relative global populations, 623 genotypes worldwide populations were included analysis. Runs computed at cut-offs 1–6 Mb, 6–12 12–24 24–48 Mb > 48 using R package detectRUNS. Golden Helix SVS program investigate Results A total 121,399 with mean number per animal breed ranging 800 (African White Dorper) 15,097 (Australian Poll Dorset) obtained. Analysis according their size showed that, for all majority detected short (1–6 Mb) category (88.2%). Most animals had no Mb. Of Nguni Blackhead Persian displayed high based inbreeding (F ) 0.31 ± 0.05 0.04, respectively. Highest incidence common SNP across observed on chromosome 10 over 250 incidences ROHs. Mean proportion SNPs island ranged 0.02 0.15 (island ROH224 23) 0.13 0.29 ROH175 15). Seventeen (17) single (unique islands). MacArthur Merino (MCM) population five unique followed three each whilst Mutton Merino, SA Vital Swakara, Karakul, Dorset Horn Chinese one island. Genes within associated predominantly metabolic immune response predomestic such as presence absence horns. Conclusions Overall, patterns this corresponds history implied exposed under study.

Language: Английский

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Trajectory of livestock genomics in South Asia: A comprehensive review

Gene, Journal Year: 2022, Volume and Issue: 843, P. 146808 - 146808

Published: Aug. 13, 2022

Language: Английский

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Challenges in quantifying genome erosion for conservation

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 26, 2022

Massive defaunation and high extinction rates have become characteristic of the Anthropocene. Genetic effects population decline can lead populations into an vortex, where declining show lower genetic fitness, in turn leading to still. The fitness a due shrinking gene pool is known as erosion. Three different types erosion are highlighted this review: overall homozygosity, load runs homozygosity (ROH), which indicative inbreeding. ability quantify could be very helpful tool for conservationists, it provide them with objective, quantifiable measure use assessment species at risk extinction. link between conservation status should more apparent. Currently, no clear correlation observed current However, quantities wild populations, especially those dealing habitat fragmentation decline, may early signs deteriorating populations. Whole genome sequencing data way forward Extra screening steps hybridization included, since they potentially great impact on fitness. This way, information yielded from sequence conservationists objective method complexity quantification asks consensus bridging science its applications, remains challenging.

Language: Английский

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