Dataset Information

Fine-mapping and identification of candidate causal genes for tail length in the Merinolandschaf breed.

ABSTRACT: Docking the tails of lambs in long-tailed sheep breeds is a common practice worldwide. But this practice is associated with pain. Breeding for a shorter tail could offer an alternative. Therefore, this study aimed to analyze the natural tail length variation in the Merinolandschaf and to identify causal alleles for the short tail phenotype segregating within long-tailed breeds. We used SNP-based association analysis and haplotype-based mapping in 362 genotyped (Illumina OvineSNP50) and phenotyped Merinolandschaf lambs. Genome-wide significant regions were capture sequenced in 48 lambs and comparatively analyzed in various long and short-tailed sheep breeds and wild sheep subspecies. Here we show a SNP located in the first exon of HOXB13 and a SINE element located in the promotor of HOXB13 as promising candidates. These results enable more precise breeding towards shorter tails, improve animal welfare by amplification of ancestral alleles and contribute to a better understanding of differential embryonic development.

SUBMITTER: Lagler DK

PROVIDER: S-EPMC9448734 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Fine-mapping and identification of candidate causal genes for tail length in the Merinolandschaf breed.

Lagler Dominik Karl DK Hannemann Elisabeth E Eck Kim K Klawatsch Jürgen J Seichter Doris D Russ Ingolf I Mendel Christian C Lühken Gesine G Krebs Stefan S Blum Helmut H Upadhyay Maulik M Medugorac Ivica I

Communications biology 20220906 1

Docking the tails of lambs in long-tailed sheep breeds is a common practice worldwide. But this practice is associated with pain. Breeding for a shorter tail could offer an alternative. Therefore, this study aimed to analyze the natural tail length variation in the Merinolandschaf and to identify causal alleles for the short tail phenotype segregating within long-tailed breeds. We used SNP-based association analysis and haplotype-based mapping in 362 genotyped (Illumina OvineSNP50) and phenotype ...[more]

PMID: 36068271

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Project description:Heritable diseases often manifest in a highly tissue-specific manner, with different disease loci mediated by genes in distinct tissues or cell types. We propose Tissue-Gene Fine-Mapping (TGFM), a fine-mapping method that infers the posterior probability (PIP) for each gene-tissue pair to mediate a disease locus by analyzing GWAS summary statistics (and in-sample LD) and leveraging eQTL data from diverse tissues to build cis-predicted expression models; TGFM also assigns PIPs to causal variants that are not mediated by gene expression in assayed genes and tissues. TGFM accounts for both co-regulation across genes and tissues and LD between SNPs (generalizing existing fine-mapping methods), and incorporates genome-wide estimates of each tissue's contribution to disease as tissue-level priors. TGFM was well-calibrated and moderately well-powered in simulations; unlike previous methods, TGFM was able to attain correct calibration by modeling uncertainty in cis-predicted expression models. We applied TGFM to 45 UK Biobank diseases/traits (average N=316K) using eQTL data from 38 GTEx tissues. TGFM identified an average of 147 PIP > 0.5 causal genetic elements per disease/trait, of which 11% were gene-tissue pairs. Implicated gene-tissue pairs were concentrated in known disease-critical tissues, and causal genes were strongly enriched in disease-relevant gene sets. Causal gene-tissue pairs identified by TGFM recapitulated known biology (e.g., TPO-thyroid for Hypothyroidism), but also included biologically plausible novel findings (e.g., SLC20A2-artery aorta for Diastolic blood pressure). Further application of TGFM to single-cell eQTL data from 9 cell types in peripheral blood mononuclear cells (PBMC), analyzed jointly with GTEx tissues, identified 30 additional causal gene-PBMC cell type pairs at PIP > 0.5-primarily for autoimmune disease and blood cell traits, including the well-established role of CTLA4 in CD8+ T cells for All autoimmune disease. In conclusion, TGFM is a robust and powerful method for fine-mapping causal tissues and genes at disease-associated loci.

Project description:BackgroundThe southern root-knot nematode (Meloidogyne incognita; RKN) is one of the most important economic pests of Upland cotton (Gossypium hirsutum L.). Host plant resistance, the ability of a plant to suppress nematode reproduction, is the most economical, practical, and environmentally sound method to provide protection against this subterranean pest. The resistant line Auburn 623RNR and a number of elite breeding lines derived from it remain the most important source of root-knot nematode (RKN) resistance. Prior genetic analysis has identified two epistatically interacting RKN resistance QTLs, qMi-C11 and qMi-C14, affecting gall formation and RKN reproduction, respectively.ResultsWe developed a genetic population segregating only for the qMi-C14 locus and evaluated the genetic effects of this QTL on RKN resistance in the absence of the qMi-C11 locus. The qMi-C14 locus had a LOD score of 12 and accounted for 24.5 % of total phenotypic variation for egg production. In addition to not being significantly associated with gall formation, this locus had a lower main effect on RKN reproduction than found in our previous study, which lends further support to evidence of epistasis with qMi-C11 in imparting RKN resistance in the Auburn 623RNR source. The locus qMi-C14 was fine-mapped with the addition of 16 newly developed markers. By using the reference genome sequence of G. raimondii, we identified 20 candidate genes encoding disease resistance protein homologs in the newly defined 2.3 Mb region flanked by two SSR markers. Resequencing of an RKN resistant and susceptible G. hirsutum germplasm revealed non-synonymous mutations in only four of the coding regions of candidate genes, and these four genes are consequently of high interest.ConclusionsOur mapping results validated the effects of the qMi-C14 resistance locus, delimiting the QTL to a smaller region, and identified tightly linked SSR markers to improve the efficiency of marker-assisted selection. The candidate genes identified warrant functional studies that will help in identifying and characterizing the actual qMi-C14 defense gene(s) against root-knot nematodes.

Dataset Information

Fine-mapping and identification of candidate causal genes for tail length in the Merinolandschaf breed.

Publications

Fine-mapping and identification of candidate causal genes for tail length in the Merinolandschaf breed.

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