Dataset Information

Genome-wide association study and scan for signatures of selection point to candidate genes for body temperature maintenance under the cold stress in Siberian cattle populations.

ABSTRACT: BACKGROUND:Design of new highly productive livestock breeds, well-adapted to local climatic conditions is one of the aims of modern agriculture and breeding. The genetics underlying economically important traits in cattle are widely studied, whereas our knowledge of the genetic mechanisms of adaptation to local environments is still scarce. To address this issue for cold climates we used an integrated approach for detecting genomic intervals related to body temperature maintenance under acute cold stress. Our approach combined genome-wide association studies (GWAS) and scans for signatures of selection applied to a cattle population (Hereford and Kazakh Whiteheaded beef breeds) bred in Siberia. We utilized the GGP HD150K DNA chip containing 139,376 single nucleotide polymorphism markers. RESULTS:We detected a single candidate region on cattle chromosome (BTA)15 overlapping between the GWAS results and the results of scans for selective sweeps. This region contains two genes, MSANTD4 and GRIA4. Both genes are functional candidates to contribute to the cold-stress resistance phenotype, due to their indirect involvement in the cold shock response (MSANTD4) and body thermoregulation (GRIA4). CONCLUSIONS:Our results point to a novel region on BTA15 which is a candidate region associated with the body temperature maintenance phenotype in Siberian cattle. The results of our research and the follow up studies might be used for the development of cattle breeds better adapted to cold climates of the Russian Federation and other Northern countries with similar climates.

SUBMITTER: Igoshin AV

PROVIDER: S-EPMC6421640 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Genome-wide association study and scan for signatures of selection point to candidate genes for body temperature maintenance under the cold stress in Siberian cattle populations.

Igoshin Alexander V AV Yurchenko Andrey A AA Belonogova Nadezhda M NM Petrovsky Dmitry V DV Aitnazarov Ruslan B RB Soloshenko Vladimir A VA Yudin Nikolay S NS Larkin Denis M DM

BMC genetics 20190318 Suppl 1

<h4>Background</h4>Design of new highly productive livestock breeds, well-adapted to local climatic conditions is one of the aims of modern agriculture and breeding. The genetics underlying economically important traits in cattle are widely studied, whereas our knowledge of the genetic mechanisms of adaptation to local environments is still scarce. To address this issue for cold climates we used an integrated approach for detecting genomic intervals related to body temperature maintenance under ...[more]

PMID: 30885142

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Project description:BackgroundThousands of years of natural and artificial selection have resulted in indigenous cattle breeds that are well-adapted to the environmental challenges of their local habitat and thereby are considered as valuable genetic resources. Understanding the genetic background of such adaptation processes can help us design effective breeding objectives to preserve local breeds and improve commercial cattle. To identify regions under putative selection, GGP HD 150 K single nucleotide polymorphism (SNP) arrays were used to genotype 106 individuals representing five Swedish breeds i.e. native to different regions and covering areas with a subarctic cold climate in the north and mountainous west, to those with a continental climate in the more densely populated south regions.ResultsFive statistics were incorporated within a framework, known as de-correlated composite of multiple signals (DCMS) to detect signatures of selection. The obtained p-values were adjusted for multiple testing (FDR?<?5%), and significant genomic regions were identified. Annotation of genes in these regions revealed various verified and novel candidate genes that are associated with a diverse range of traits, including e.g. high altitude adaptation and response to hypoxia (DCAF8, PPP1R12A, SLC16A3, UCP2, UCP3, TIGAR), cold acclimation (AQP3, AQP7, HSPB8), body size and stature (PLAG1, KCNA6, NDUFA9, AKAP3, C5H12orf4, RAD51AP1, FGF6, TIGAR, CCND2, CSMD3), resistance to disease and bacterial infection (CHI3L2, GBP6, PPFIBP1, REP15, CYP4F2, TIGD2, PYURF, SLC10A2, FCHSD2, ARHGEF17, RELT, PRDM2, KDM5B), reproduction (PPP1R12A, ZFP36L2, CSPP1), milk yield and components (NPC1L1, NUDCD3, ACSS1, FCHSD2), growth and feed efficiency (TMEM68, TGS1, LYN, XKR4, FOXA2, GBP2, GBP5, FGD6), and polled phenotype (URB1, EVA1C).ConclusionsWe identified genomic regions that may provide background knowledge to understand the mechanisms that are involved in economic traits and adaptation to cold climate in cattle. Incorporating p-values of different statistics in a single DCMS framework may help select and prioritize candidate genes for further analyses.

Project description:Yanbian cattle is inhabitant of North of China, exhibiting many phenotypic features, such as long, dense body hair, and abundant intramuscular fat, designed to combat the extreme cold climate adaption. In the current study, we studied the cold tolerance of nine Yanbian cattle by whole genome resequencing and compared with African tropical cattle, N'Dama, as a control group. Yanbian cattle was aligned to the Bos taurus reference genome (ARS-UCD1.2) yielding an average of 10.8 fold coverage. The positive selective sweep analysis for the cold adaption in Yanbian cattle were analyzed using composite likelihood ratio (CLR) and nucleotide diversity (??), resulting in 292 overlapped genes. The strongest selective signal was found on BTA16 with potential mutation in CORT gene, a regulatory gene of primary hormone in the hypothalamic-pituitary-adrenal (HPA) axis, is reported to be associated with the cold stress, representedfour missense mutations (c.269C > T, p.Lys90Ile; c.251A > G, p.Glu84Gly; c.112C > T, p.Pro38Ser; c.86G > A, p.Pro29His). Meanwhile another gene on BTA6, showed significantly higher selective sweep signals for a cold adapted trait for hair follicle and length development, FGF5 (fibroblast growth factor 5) with a missense mutation (c.191C > T, p.Ser64Phe). Moreover, cold adapted Yanbian cattle was statistically compared with the hot adapted N'Dama cattle, a taurine cattle reported to show superior heat tolerance than zebu cattle, making them better adapted to the hot regions of Africa. XP-CLR, Fst, and ?? ratio were used to compare both breeds, yielding 487, 924, and 346 genes respectively. Among the 12 overlapped genes, (CD36) (c.638A > G, p.Lys 213Arg) involved in fat digestion and absorption plays an important role in membrane transport of long-chain fatty acid and its expression could increase in cold exposure. Henceforth, our study provides a novel genetic insights into the cold climate adaptation of Yanbian cattle and identified three candidate genes (CORT, FGF5, and CD36), which can add to an understanding of the cold climate adaptation of Yanbian cattle.

Project description:BACKGROUND: Since the times of domestication, cattle have been continually shaped by the influence of humans. Relatively recent history, including breed formation and the still enduring enormous improvement of economically important traits, is expected to have left distinctive footprints of selection within the genome. The purpose of this study was to map genome-wide selection signatures in ten cattle breeds and thus improve the understanding of the genome response to strong artificial selection and support the identification of the underlying genetic variants of favoured phenotypes. We analysed 47,651 single nucleotide polymorphisms (SNP) using Cross Population Extended Haplotype Homozygosity (XP-EHH). RESULTS: We set the significance thresholds using the maximum XP-EHH values of two essentially artificially unselected breeds and found up to 229 selection signatures per breed. Through a confirmation process we verified selection for three distinct phenotypes typical for one breed (polledness in Galloway, double muscling in Blanc-Bleu Belge and red coat colour in Red Holstein cattle). Moreover, we detected six genes strongly associated with known QTL for beef or dairy traits (TG, ABCG2, DGAT1, GH1, GHR and the Casein Cluster) within selection signatures of at least one breed. A literature search for genes lying in outstanding signatures revealed further promising candidate genes. However, in concordance with previous genome-wide studies, we also detected a substantial number of signatures without any yet known gene content. CONCLUSIONS: These results show the power of XP-EHH analyses in cattle to discover promising candidate genes and raise the hope of identifying phenotypically important variants in the near future. The finding of plausible functional candidates in some short signatures supports this hope. For instance, MAP2K6 is the only annotated gene of two signatures detected in Galloway and Gelbvieh cattle and is already known to be associated with carcass weight, back fat thickness and marbling score in Korean beef cattle. Based on the confirmation process and literature search we deduce that XP-EHH is able to uncover numerous artificial selection targets in subpopulations of domesticated animals.

Project description:Selective breeding can lead to genetic diversity and diverse phenotypes in farm animals. Analysis of the genomic regions under selection can provide important insights into the genetic basis of complex traits. In this study, a high-density SNP array was used for analysis of genome selection signatures in Chinese Wagyu cattle. In total, we obtained 478,903 SNPs and 24,820 no-overlap regions for |iHS| (integrated haplotype score) estimations. Under the threshold of the top 1%, 239 regions were finally identified as candidate selected regions and 162 candidate genes were found based on the UMD3.1 genome assembly. These genes were reported to be associated with fatty acids, such as Bos taurus nitric oxide synthase 1 adaptor protein (NOS1AP), Bos taurus hydroxysteroid 17-beta dehydrogenase 7 (HSD17B7), Bos taurus WD repeat domain 7 (WDR7), Bos taurus ELOVL fatty acid elongase 2 (ELOVL2), Bos taurus calpain 1 (CAPN1), Bos taurus parkin RBR E3 ubiquitin protein ligase (PRKN, also known as PARK2), Bos taurus mitogen-activated protein kinase kinase 6 (MAP2K6), meat quality, including Bos taurus ADAM metallopeptidase domain 12 (ADAM12), Bos taurus 5'-aminolevulinate synthase 1 (ALAS1), Bos taurus small integral membrane protein 13 (SMIM13) and Bos taurus potassium two pore domain channel subfamily K member 2 (KCNK2), growth, and developmental traits, such as Bos taurus insulin like growth factor 2 receptor (IGF2R), Bos taurus RAR related orphan receptor A (RORA), Bos taurus fibroblast growth factor 14 (FGF14), Bos taurus paired box 6 (PAX6) and Bos taurus LIM homeobox 6 (LHX6). In addition, we identified several genes that are associated with body size and weight, including Bos taurus sorting nexin 29 (SNX29), Bos taurus zinc finger imprinted 2 (ZIM2), Bos taurus family with sequence similarity 110 member A (FAM110A), immune system, including Bos taurus toll like receptor 9 (TLR9), Bos taurus TAFA chemokine like family member 1 (TAFA1), Bos taurus glutathione peroxidase 8 (putative) (GPX8), Bos taurus interleukin 5 (IL5), Bos taurus PR domain containing 9 (PRDM9), Bos taurus glutamate ionotropic receptor kainate type subunit 2 (GRIK2) and feed intake efficiency, Bos taurus sodium voltage-gated channel alpha subunit 9 (SCN9A), Bos taurus relaxin family peptide/INSL5 receptor 4 (RXFP4), Bos taurus RNA polymerase II associated protein 3 (RPAP3). Moreover, four GO terms of biological regulation (GO:0009987, GO:0008152) and metabolic process (GO:0003824, GO:0005488) were found based on these genes. In addition, we found that 232 candidate regions (~18 Mb) overlapped with the Quantitative trait loci (QTL)regions extracted from cattle QTLdb. Our findings imply that many genes were selected for important traits in Chinese Wagyu cattle. Moreover, these results can contribute to the understanding of the genetic basis of the studied traits during the formation of this population.

Project description:High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude.

Project description:Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome) had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs) for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ?10% in clone HB3), and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%), indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing selection are now prioritized for functional study.

Dataset Information

Genome-wide association study and scan for signatures of selection point to candidate genes for body temperature maintenance under the cold stress in Siberian cattle populations.

Publications

Genome-wide association study and scan for signatures of selection point to candidate genes for body temperature maintenance under the cold stress in Siberian cattle populations.

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