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Taurine and Indicine Haplotype Representation in Advanced Generation Individuals From Three American Breeds

ABSTRACT: Development of the American Breeds of beef cattle began in the 1920s as breeders and U. S. Experiment Station researchers began to create Bos taurus taurus × Bos taurus indicus hybrids using Brahman as the B. t. indicus source. By 1954, U.S. Breed Associations had been formed for Brangus (5/8 Angus × 3/8 Brahman), Beefmaster (½ Brahman × ¼ Shorthorn × ¼ Hereford), and Santa Gertrudis (5/8 Shorthorn × 3/8 Brahman). While these breeds were developed using mating designs expected to create base generation animals with the required genome contributions from progenitor breeds, each association has now registered advanced generation animals in which selection or drift may have caused the realized genome compositions to differ from initial expected proportions. The availability of high-density SNP genotypes for 9,161 Brangus, 3,762 Beefmaster, and 1,942 Santa Gertrudis animals allowed us to compare the realized genomic architectures of breed members to the base generation expectations. We used RFMix to estimate local ancestry and identify genomic regions in which the proportion of Brahman ancestry differed significantly from a priori expectations. For all three breeds, lower than expected levels of Brahman composition were found genome-wide, particularly in early-generation animals where we demonstrate that selection on beef production traits was likely responsible for the taurine enrichment. Using a proxy for generation number, we also contrasted the genomes of early- and advanced-generation animals and found that the indicine composition of the genome has increased with generation number likely due to selection on adaptive traits. Many of the most-highly differentiated genomic regions were breed specific, suggesting that differences in breeding objectives and selection intensities exist between the breeds. Global ancestry estimation is commonly performed in admixed animals to control for stratification in association studies. However, local ancestry estimation provides the opportunity to investigate the evolution of specific chromosomal segments and estimate haplotype effects on trait variation in admixed individuals. Investigating the genomic architecture of the American Breeds not only allows the estimation of indicine and taurine genome proportions genome-wide, but also the locations within the genome where either taurine or indicine alleles confer a selective advantage.

SUBMITTER: Crum T

PROVIDER: S-EPMC8558500 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The primary goal of cattle genomics is the identification of genome-wide polymorphism associated with economically important traits. The bovine genome sequencing project was completed in 2009. Since then, using massively parallel sequencing technologies, a large number of Bos taurus cattle breeds have been resequenced and scanned for genome-wide polymorphisms. As a result, a substantial number of single nucleotide polymorphisms (SNPs) have been discovered across European Bos taurus genomes, whereas extremely less number of SNPs are cataloged for Bos indicus breeds. In this study, we performed whole-genome resequencing, reference-based mapping, functional annotation and gene enrichment analysis of 20 sires representing eleven important Bos indicus (indicine) breeds of Pakistan. The breeds sequenced here include: Sahiwal, Red Sindhi, Tharparkar and Cholistani (tropically adapted dairy and dual purpose breeds), Achai, Bhagnari, Dajal and Lohani (high altitude adapted dual and drought purpose breeds); Dhanni, Hisar Haryana and Gabrali (dairy and light drought purpose breeds). A total of 17.4 billion QC passed reads were produced using BGISEQ-500 next generation sequencing platform to generate 9 to 27-fold genome coverage (average ~16×) for each of the 20 sequenced sires. A total of 67,303,469 SNPs were identified, of which 3,850,365 were found novel and 1,083,842 insertions-deletions (InDels) were detected across the whole sequenced genomes (491,247 novel). Comparative analysis using coding region SNPs revealed a close relationship between the best milking indicine breeds; Red Sindhi and Sahiwal. On the other hand, Bhagnari and Tharparkar being popular for their adaptation to dry and extremely hot climates were found to share the highest number of SNPs. Functional annotation identified a total of 3,194 high-impact (disruptive) SNPs and 745 disruptive InDels (in 275 genes) that may possibly affect economically important dairy and beef traits. Functional enrichment analysis was performed and revealed that high or moderate impact variants in wingless-related integration site (Wnt) and vascular smooth muscle contraction (VSMC) signaling pathways were significantly over-represented in tropically adapted heat tolerant Pakistani-indicine breeds. On the other hand, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) signaling pathways were found over-represented in highland adapted Pakistani-indicine breeds. Similarly, the ECM-receptor interaction and Jak-STAT signaling pathway were significantly enriched in dairy and beef purpose Pakistani-indicine cattle breeds. The Toll-like receptor signaling pathway was significantly enriched in most of the Pakistani-indicine cattle. Therefore, this study provides baseline data for further research to investigate the molecular mechanisms of major traits and to develop potential genomic markers associated with economically important breeding traits, particularly in indicine cattle.

Project description:ImportanceIdentifying gaps in inclusivity of Indigenous individuals is key to diversifying academic medical programs, increasing American Indian and Alaska Native representation, and improving disparate morbidity and mortality outcomes in American Indian and Alaska Native populations.ObjectiveTo examine representation of American Indian and Alaska Native individuals at different stages in the 2018-2019 academic medical training continuum and trends (2011-2020) of American Indian and Alaska Native representation in residency specialties.Design, setting, and participantsA cross-sectional, population-based analysis was conducted using self-reported race and ethnicity data on trainees from the Association of American Medical Colleges (2018), the Accreditation Council for Graduate Medical Education (2011-2018), and the US Census (2018). Data were analyzed between February 18, 2020, and March 4, 2021.ExposuresEnrolled trainees at specific stages of medical training.Main outcomes and measuresThe primary outcome was the odds of representation of American Indian and Alaska Native individuals at successive academic medical stages in 2018-2019 compared with White individuals. Secondary outcomes comprised specialty-specific proportions of American Indian and Alaska Native residents from 2011 to 2020 and medical specialty-specific proportions of American Indian and Alaska Native physicians in 2018. Fisher exact tests were performed to calculate the odds of American Indian and Alaska Native representation at successive stages of medical training. Simple linear regressions were performed to assess trends across residency specialties.ResultsThe study data contained a total of 238 974 607 White and American Indian and Alaska Native US citizens, 24 795 US medical school applicants, 11 242 US medical school acceptees, 10 822 US medical school matriculants, 10 917 US medical school graduates, 59 635 residents, 518 874 active physicians, and 113 168 US medical school faculty. American Indian and Alaska Native individuals had a 63% lower odds of applying to medical school (odds ratio [OR], 0.37; 95% CI, 0.31-0.45) and 48% lower odds of holding a full-time faculty position (OR, 0.52; 95% CI, 0.44-0.62) compared with their White counterparts, yet had 54% higher odds of working in a residency specialty deemed as a priority by the Indian Health Service (OR, 1.54; 95% CI, 1.09-2.16). Of the 33 physician specialties analyzed, family medicine (0.55%) and pain medicine (0.46%) had more than an average proportion (0.41%) of American Indian and Alaska Native physicians compared with their representation across all specialties.Conclusions and relevanceThis cross-sectional study noted 2 distinct stages in medical training with significantly lower representation of American Indian and Alaska Native compared with White individuals. An actionable framework to guide academic medical institutions on their Indigenous diversification and inclusivity efforts is proposed.

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Taurine and Indicine Haplotype Representation in Advanced Generation Individuals From Three American Breeds

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