Autosomal SNPs Research Articles

A genome-wide association study for recurrent laryngeal neuropathy in the Thoroughbred horse identifies a candidate gene that regulates myelin structure.

Equine recurrent laryngeal neuropathy (RLN) is an economically important upper respiratory tract (URT) disease with a genetic contribution to risk, but genetic variants independent of height have not been identified for Thoroughbreds. The method of clinical assessment for RLN is critical to accurately phenotype groups for genetic studies. To identify genetic risk loci for RLN in Thoroughbreds in a genome-wide association study (GWAS) following high-resolution phenotyping. Case-control. Thoroughbred horses were characterised as RLN cases and controls using resting and exercising URT endoscopic examinations and laryngeal ultrasonography, with the case-cohort supplemented using a questionnaire. Genotypes for 43 831 autosomal single-nucleotide polymorphisms (SNPs) from n = 235 horses (n = 110 cases; n = 125 controls) were used to estimate trait heritability and identify significantly associated SNPs in a GWAS. Haplotypes were examined in cases and controls and risk allele frequencies were examined in a population cohort (n = 3126). Heritability was h2 = 0.30 including sex and 5PCs as covariates. A SNP on ECA20 located between candidate genes, DAAM2 and LRFN2, was significantly associated with RLN. Six index SNPs with allelic effect sizes OR = 1.5-2.9 were identified on ECA1, ECA14, and ECA20 close to candidate genes ATPA10, KCNN2, and TFAP2A. Eleven ECA20 SNPs defined seven haplotypes with homozygous H2/H2 horses having a 3.1× higher risk of RLN. Risk alleles segregate in the population, and stallions are carriers. The main study population was young. Horses in the control group had no evidence of RLN as 2- or 3-year olds but may have developed RLN later. Genetic markers for RLN were identified which may be useful for the development of a polygenic risk score. Candidate genes with functions in neuropathies may further the understanding of RLN pathobiology.

Genomic Diversity of U.S. Katahdin Hair Sheep.

In the late 1950s, Katahdin hair sheep were developed as a composite breed of medium size and moderate prolificacy, with potential to express resistance to gastrointestinal nematodes. With increasing popularity and the recent adoption of genomic prediction in their genetic evaluation, there is a risk of decreasing variation with selection based on genomically enhanced estimated breeding values. While Katahdin pedigrees are readily available for monitoring diversity, they may not capture the entirety of genetic relationships. We aimed to characterise the genomic population structure and diversity present in the breed, and how these impact the size of a reference population necessary to achieve accurate genomic predictions. Genotypes of Katahdin sheep from 81 member flocks in the National Sheep Improvement Program (NSIP) were used. After quality control, there were 9704 animals and 31,984 autosomal single nucleotide polymorphisms analysed. Population structure was minimal as a single ancestral population explained 99.9% of the genetic variation among animals. The current Ne was estimated to be 150, and despite differences in trait heritabilities, the effect of Ne on the accuracy of genomic predictions suggested the breed should aim for a reference population size of 15,000 individuals. The average degree of inbreeding estimated from runs of homozygosity (ROH) was 16.6% ± 4.7. Four genomic regions of interest, previously associated with production traits, contained ROH shared among > 50% of the breed. Based on four additional methods, average genomic inbreeding coefficients ranged from 0.011 to 0.012. The current population structure and diversity of the breed reflects genetic connectedness across flocks due to the sharing of animals. Shared regions of ROH should be further explored for incorporation of functional effects into genomic predictions to increase selection gains. Negative impacts on genetic diversity due to genomic selection are not of immediate concern for Katahdin sheep engaged in NSIP.

Private detection of relatives in forensic genomics using homomorphic encryption.

Forensic analysis heavily relies on DNA analysis techniques, notably autosomal Single Nucleotide Polymorphisms (SNPs), to expedite the identification of unknown suspects through genomic database searches. However, the uniqueness of an individual's genome sequence designates it as Personal Identifiable Information (PII), subjecting it to stringent privacy regulations that can impede data access and analysis, as well as restrict the parties allowed to handle the data. Homomorphic Encryption (HE) emerges as a promising solution, enabling the execution of complex functions on encrypted data without the need for decryption. HE not only permits the processing of PII as soon as it is collected and encrypted, such as at a crime scene, but also expands the potential for data processing by multiple entities and artificial intelligence services. This study introduces HE-based privacy-preserving methods for SNP DNA analysis, offering a means to compute kinship scores for a set of genome queries while meticulously preserving data privacy. We present three distinct approaches, including one unsupervised and two supervised methods, all of which demonstrated exceptional performance in the iDASH 2023 Track 1 competition. Our HE-based methods can rapidly predict 400 kinship scores from an encrypted database containing 2000 entries within seconds, capitalizing on advanced technologies like Intel AVX vector extensions, Intel HEXL, and Microsoft SEAL HE libraries. Crucially, all three methods achieve remarkable accuracy levels (ranging from 96% to 100%), as evaluated by the auROC score metric, while maintaining robust 128-bit security. These findings underscore the transformative potential of HE in both safeguarding genomic data privacy and streamlining precise DNA analysis. Results demonstrate that HE-based solutions can be computationally practical to protect genomic privacy during screening of candidate matches for further genealogy analysis in Forensic Genetic Genealogy (FGG).

Population Structure and Selection Signatures in Chinese Indigenous Zhaotong Pigs Revealed by Whole-Genome Resequencing.

Zhaotong pig (ZTP) is a Chinese indigenous pig breed in Yunnan Province, known for its unique body shape and appearance, good meat quality, strong foraging ability, and adaptability. However, there is still a lack of research on its genome. In order to investigate the genetic diversity, population structure, and selection signatures of the breed, we conducted a comprehensive analysis by resequencing on 30 ZTPs and comparing them with genomic data from 10 Asian wild boars (AWBs). A total of 45,514,452 autosomal SNPs were detected in the 40 pigs, and 23,649,650 SNPs were retained for further analysis after filtering. The HE, HO, PN, MAF, π, and Fis values were calculated to evaluate the genetic diversity, and the results showed that ZTPs had higher genetic diversity and lower inbreeding coefficient compared with AWBs. Population structure was analyzed using NJ tree, PCA, ADMIXTURE, and LD methods. It was found that ZTPs were population independent of AWBs and had a lower LD decay compared to AWBs. Moreover, the results of the IBS genetic distance and G matrix showed that most of the individuals had large genetic distances and distant genetic relationships in ZTPs. Selection signatures were detected between ZTPs and AWBs by using two methods, FST and π ratio. Totals of 1104 selected regions and 275 candidate genes were identified. Finally, functional enrichment analysis identified some annotated genes that might affect fat deposition (NPY1R, NPY5R, and NMU), reproduction (COL3A1, COL5A2, GLRB, TAC3, and MAP3K12), growth (STAT6 and SQOR), tooth development (AMBN, ENAM, and ODAM), and immune response (MBL2, IL1A, and DNAJA3). Our results will provide a valuable basis for the future effective protection, breeding, and utilization of ZTPs.

Paleoasian Substrate in the Gene Pool of Koryaks According to Data on Autosomal SNP Polymorphism and Y-Chromosome Haplogroups

The gene pool of the Koryaks was studied in comparison with other Far Eastern and Siberian peoples using a genome-wide panel of autosomal single-nucleotide polymorphic markers and Y-chromosome markers. The results of analyzing the frequencies of autosomal SNPs using various methods, the similarity in the composition of Y-chromosome haplogroups and YSTR haplotypes indicate that the gene pool of the Koryaks is as close as possible to the Chukchi one and was formed as a result of the unification of several groups whose ancestors moved from the territory of modern Yakutia and the Amur region. The two dominant Y-chromosome haplogroups of the Koryaks with different sublineages and haplotype clusters demonstrate their contacts with the Chukchi, Evens, Yukaghirs and Eskimos. Analysis of the composition of genetic components and IBD blocks on autosomes indicates the maximum genetic proximity of the Koryaks to the Chukchi. Among the Siberian populations, the Chukchi, Koryaks and Nivkhs form a separate cluster from the main group of Siberian populations, while the Chukchi and Koryaks are more closely related. Far Eastern populations are divided in full accordance with geographic localization into the northern group (Chukchi and Koryaks) and the southern group, including the Nivkhs and Udege. A more detailed analysis of the component composition of gene pools in some populations reveals components specific to them. The isolation of such components is associated with founder effects and a shift in allele frequencies for these populations. The Koryaks and Chukchi are one of the most striking examples of long-standing genetic kinship. In their populations, maximum values of the level of genomic inbreeding FROH 1.5 (0.0422, 0.0409) were found, which is natural due to their relative isolation.

Contrasting Genomic Diversity and Inbreeding Levels Among Two Closely Related Falcon Species With Overlapping Geographic Distributions.

Genomic resources are valuable to examine historical demographic patterns and their effects to better inform management and conservation of threatened species. We evaluated population trends and genome-wide variation in the near-threatened Orange-breasted Falcon (Falco deiroleucus) and its more common sister species, the Bat Falcon (F. rufigularis), to explore how the two species differ in genomic diversity as influenced by their contrasting long-term demographic histories. We generated and aligned whole genome resequencing data for 12 Orange-breasted Falcons and 9 Bat Falcons to an annotated Gyrfalcon (F. rusticolus) reference genome that retained approximately 22.4 million biallelic autosomal SNPs (chromosomes 1-22). Our analyses indicated much lower genomic diversity in Orange-breasted Falcons compared to Bat Falcons. All sampled Orange-breasted Falcons were significantly more inbred than the sampled Bat Falcons, with values similar to those observed in island-mainland species comparisons. The distribution of runs of homozygosity showed variation suggesting long-term low population size and the possibility of bottlenecks in Orange-breasted Falcons contrasting with consistently larger populations in Bat Falcons. Analysis of genetic load suggests that Orange-breasted Falcons are less likely to experience inbreeding depression than Bat Falcons due to reduced inbreeding load but are at elevated risk from fixation of deleterious gene variants and perhaps a reduced adaptive potential. These genomic analyses highlight differences in the historical demography of two closely related species that have influenced their current genomic diversity and should result in differing strategies for their continued conservation.

Enhancing testing efficacy of high-density SNP microarrays to distinguish pedigrees belonging to the same kinship class

Kinship testing, which involves genotyping genetic markers and comparing their profiles between individuals, holds significant applications in forensic science. However, the prevalent use of independent markers often lacks the discriminatory power to distinguish pedigrees belong to the same kinship class. While numerous studies have attempted to address this challenge through diverse approaches, the testing efficacy of high-density SNP microarrays in combination with the likelihood approach remains unclear.In this study, we further explored the utilization of linked autosomal SNPs derived from microarrays with the likelihood approach. Several SNP panels with differing numbers of loci were developed and putative pedigrees were constructed to evaluated to test their efficacy in distinguishing second-degree relationships, including grandparent-grandchild, half-siblings, and avuncular. Our findings indicate that the use of high-density SNP microarrays is theoretically feasible for discriminating second-degree relationships, with balanced classification rates ranging from 0.444 to 0.853.Moreover, to optimize the practical effectiveness of discriminating pedigrees belonging to the same kinship class, several other aspects such as adding additional SNPs or an additional relative and examining the effects of genotype errors and population selection were discussed. Our results revealed that the employment of denser marker sets with more accurate genotyping methods may be beneficial. Additionally, the inclusion of additional relatives and the selection of an appropriate reference population also appear to be crucial factors for enhancing the accuracy of kinship testing.In conclusion, our study provides insights into the potential of high-density SNPs in kinship testing and highlights the need for further optimization and examination into various factors that may contribute to enhancing testing efficacy.

Traces of Paleolithic expansion in the Nivkh gene pool based on data on autosomal SNP and Y chromosome polymorphism.

The Nivkhs are a small ethnic group indigenous of the Russian Far East, living in the Khabarovsk Territory and on Sakhalin Island, descending from the ancient inhabitants of these territories. In the Nivkhs, a specific Sakhalin-Amur anthropological type is prevalent. They are quite isolated, due to long isolation from contacts with other peoples. The gene pool of the Nivkhs and other Far Eastern and Siberian populations was characterized using a genome-wide panel of autosomal single-nucleotide polymorphic markers and Y chromosome haplogroups. Bioinformatic processing of frequencies of autosomal SNPs, Y chromosome haplogroups and YSTR haplotypes showed that the Nivkh gene pool is very different from the other populations'. Analysis of the SNP frequencies using the PCA method divided the Far Eastern populations in full accordance with the territories of their residence into the northern group of the Chukchi and Koryaks and the southern group, including the Nivkhs and Udege. The remoteness of the Nivkhs coincides with their geographic localization, with the Nivkhs and Udege demonstrating the greatest kinship. The Nivkhs have a specific component of their gene pool, which is present with much less frequency in the Udege and Transbaikal Evenks. According to the IBD blocks, the genotypes of the Nivkhs show a very small percentage of coincidence with the Udege, Koryaks, Evenks and Chukchi, the value of which is the lowest compared to the IBD blocks among all other Siberian populations. The Nivkh-specific composition of haplogroups and YSTR haplotypes was shown. In the Nivkhs, the C2a1 haplogroup is divided into three sublines, which have a fairly ancient origin and are associated with the ancestors of modern northern Mongoloids. The Nivkh haplogroup O2a1b1a2a-F238 is found among residents of China and Myanmar. The Q1a1a1-M120 line is represented among the Nivkhs, Koryaks, Evenks and Yukaghirs. Phylogenetic analysis of individual Y chromosomal haplogroups demonstrated the closeness of the Nivkh gene pool with the ancient population of the Amur and Okhotsk regions, the Koryaks, the Tungus peoples and the population of Southeast Asia. The Nivkh gene pool confirms the relative smallness of their ancestral groups without mixing with other populations.

Genetic diversity of North African populations in the 17q21 genomic region.

The demographic history of human populations in North Africa has been characterized by complex migration processes that have determined the current genetic structure of these populations. We examined the autosomal markers of eight sampled populations in northern Africa (Tunisia and Libya) to explore their genetic structure and to place them in a global context. We genotyped a set of 30 autosomal single-nucleotide polymorphisms (SNPs) extending 9.5Mb and encompassing the 17q21 inversion region. Our data include 403 individuals from Tunisia and Libya. To put our populations in the global context, we analyzed our data in comparison with other populations, including those of the 1000 Genomes Project. To evaluate the data, we conducted genetic diversity, principal component, STRUCTURE, and haplotype analyses. The analysis of genetic composition revealed the genetic heterogeneity of North African populations. The principal component and STRUCTURE analyses converged and revealed the intermediate position of North Africans between Europeans and Asians. Haplotypic analysis demonstrated that the normal (H1) and inverted (H2) polymorphisms in the chromosome 17q21 region occur in North Africa at frequencies similar to those found in European and Southwest Asian populations. The results highlight the complex demographic history of North Africa, reflecting the influence of genetic flow from Europe and the Near East that dates to the prehistoric period. These gene flows added to demographic factors (inbreeding, endogamy), natural factors (topography, Sahara), and cultural factors that play a role in the emergence of the diverse and heterogeneous genetic structures of North African populations. This study contributes to a better understanding of the complex structure of North African populations.

Genomic characterisation and diversity assessment of eight endangered Belgian sheep breeds

Assessing the genetic diversity of local breeds is essential for conserving these unique breeds, which may possess unique traits. This study provides the genomic characterisation of eight indigenous sheep breeds in Belgium based on pedigree and single nucleotide polymorphism (SNP) analysis. A total of 687 sheep were genotyped and were subjected to a rigorous quality control, resulting in a set of 45 978 autosomal SNPs. Pedigree analysis showed breed-average inbreeding estimates between 3.3% and 11.3%. The genomic analysis included an assessment of runs of homozygosity (ROH) to examine the genomic inbreeding coefficient, with breed-average inbreeding coefficients estimated between 4.1% and 8.5%. Runs of homozygosity islands were identified in six of the eight breeds studied, with some exhibiting an incidence of up to 58%. Interestingly, several ROH islands overlapped with other breeds included in this study, as well as with international sheep breeds. Pedigree-based effective population sizes were estimated below 100 for all breeds, whereas genomic-based effective population sizes were below 24, indicating that these eight local sheep breeds are endangered. Principal component analysis, admixture analyses, and Fst computations were used to study the population structure and genetic differences. A neighbour−joining tree using 95 international sheep breeds positioned the eight local breeds in the group of milksheep, Texel sheep and the Scandinavian breeds. Additionally, the investigation of paternal oY1 genotypes revealed diverse lineage origins within the Belgian sheep population. This study refines and deepens our knowledge about the local sheep breeds in Belgium, thereby improving their management and conservation. Moreover, as these breeds are linked to other international breeds, these insights are significant for the global scientific community.

Analyzing Runs of Homozygosity Reveals Patterns of Selection in German Brown Cattle.

An increasing trend in ancestral and classical inbreeding coefficients as well as inbreeding depression for longevity were found in the German Brown population. In addition, the proportion of US Brown Swiss genes is steadily increasing in German Browns. Therefore, the aim of the present study was to analyze the presence and genomic localization of runs of homozygosity (ROH) in order to evaluate their associations with the proportion of US Brown Swiss genes and survival rates of cows to higher lactations. Genotype data were sampled in 2364 German Browns from 258 herds. The final data set included 49,693 autosomal SNPs. We identified on average 35.996 ± 7.498 ROH per individual with a mean length of 8.323 ± 1.181 Mb. The genomic inbreeding coefficient FROH was 0.122 ± 0.032 and it decreased to 0.074, 0.031 and 0.006, when genomic homozygous segments > 8 Mb (FROH>8), >16 Mb (FROH>16) and >32 Mb (FROH>32) were considered. New inbreeding showed the highest correlation with FROH>32, whereas ancestral inbreeding coefficients had the lowest correlations with FROH>32. The correlation between the classical inbreeding coefficient and FROH was 0.572. We found significantly lower FROH, FROH>4, FROH>8 and FIS for US Brown Swiss proportions <60% compared to >80%. Cows surviving to the 2nd, 4th, 6th, 8th, and 10th lactation had lower genomic inbreeding for FROH and up to FROH>32, which was due to a lower number of ROH and a shorter average length of ROH. The strongest ROH island and consensus ROH shared by 50% of the animals was found on BTA 6 at 85-88 Mb. The genes located in this genomic region were associated with longevity (NPFFR2 and ADAMTS3), udder health and morphology (SLC4A4, NPFFR2, GC and RASSF6), milk production, milk protein percentage, coagulation properties of milk and milking speed (CSN3). On BTA 2, a ROH island was detected only in animals with <60% US Brown Swiss genes. Genes within this region are predominantly important for dual-purpose cattle breeds including Original Browns. For cows reaching more than 9 lactations, an exclusive ROH island was identified on BTA 7 with genes assumed to be associated with longevity. The analysis indicated that genomic homozygous regions important for Original Browns are still present and also ROH containing genes affecting longevity may have been identified. The breeding of German Browns should prevent any further increase in genomic inbreeding and run a breeding program with balanced weights on production, robustness and longevity.

Runs of homozygosity analysis and genomic inbreeding estimation in Sumba Ongole cattle (Bos indicus) using a BovineSNP50K BeadChip.

Runs of homozygosity (ROH) is a biocomputational technique for identifying homozygous regions in the genomics of livestock. This study aimed to determine the ROH in Sumba Ongole (SO) bulls (n = 48) using the BovineSNP50K BeadChip. GenomeStudio 2.0 software was used to generate the BovineSNP50K BeadChip output. The ROH and ROH-based inbreeding coefficients (FROH) were determined using the detect RUNS R v4.1.0 package. Using the following filtering criteria, PLINK v1.90 software was used to perform genotype quality control: (1) Individuals and single-nucleotide polymorphism (SNPs) had call rates >0.95; (2) more than 0.05 was the minor allele frequency; (3) the list contained only SNPs linked to autosomes; and (4) SNPs that strongly deviated (p < 1e-6) from Hardy-Weinberg equilibrium were removed. Subsequently, 25,252 autosomal SNP markers were included in the ROH and FROH analyses. In general, the number and length of ROH segments in pool animals were 149.77 ± 16.02 Mb and 486.13 ± 156.11 Mb, respectively. Furthermore, the ROH segments in the animals under study can be discriminated into two classes of 1-4 Mb (83.33%) and 4-8 Mb (16.67%). Subsequently, Bos taurus autosomes (BTA) 1, BTA6, and BTA14 had significant homozygous segments comprising 13 genes. Despite this, the average FROH in pool animals was 0.20 ± 0.06. These findings indicate that a recent inbreeding event in SO cattle occurred many generations ago. Furthermore, the candidate genes identified from the ROH analysis indicate phenotypic attributes associated with environmental adaptation and economic traits.

Genetic diversity of United States Rambouillet, Katahdin and Dorper sheep

BackgroundManaging genetic diversity is critically important for maintaining species fitness. Excessive homozygosity caused by the loss of genetic diversity can have detrimental effects on the reproduction and production performance of a breed. Analysis of genetic diversity can facilitate the identification of signatures of selection which may contribute to the specific characteristics regarding the health, production and physical appearance of a breed or population. In this study, breeds with well-characterized traits such as fine wool production (Rambouillet, N = 745), parasite resistance (Katahdin, N = 581) and environmental hardiness (Dorper, N = 265) were evaluated for inbreeding, effective population size (Ne), runs of homozygosity (ROH) and Wright’s fixation index (FST) outlier approach to identify differential signatures of selection at 36,113 autosomal single nucleotide polymorphisms (SNPs).ResultsKatahdin sheep had the largest current Ne at the most recent generation estimated with both the GONe and NeEstimator software. The most highly conserved ROH Island was identified in Rambouillet with a signature of selection on chromosome 6 containing 202 SNPs called in an ROH in 50 to 94% of the individuals. This region contained the DCAF16, LCORL and NCAPG genes that have been previously reported to be under selection and have biological roles related to milk production and growth traits. The outlier regions identified through the FST comparisons of Katahdin with Rambouillet and Dorper contained genes with known roles in milk production and mastitis resistance or susceptibility, and the FST comparisons of Rambouillet with Katahdin and Dorper identified genes related to wool growth, suggesting these traits have been under natural or artificial selection pressure in these populations. Genes involved in the cytokine-cytokine receptor interaction pathways were identified in all FST breed comparisons, which indicates the presence of allelic diversity between these breeds in genomic regions controlling cytokine signaling mechanisms.ConclusionsIn this paper, we describe signatures of selection within diverse and economically important U.S. sheep breeds. The genes contained within these signatures are proposed for further study to understand their relevance to biological traits and improve understanding of breed diversity.

Genomic analysis of conservation status, population structure, and admixture in local Czech and Slovak dairy goat breeds

While dairy goat production, characterized by traditional production on small farms, is an important source of income in the Czech Republic and Slovakia, locally adapted breeds have not been fully consolidated over the last 100 years due to large fluctuations in population size and inconsistent breeding programs that allowed for different crossbreeding strategies. Our main objective in this study was therefore to assess the conservation status of 4 Czech (Alpine Goat, White Shorthair, Brown Shorthair and Czech Landrace) and one Slovak (Slovak White Shorthair) local goat breeds, to analyze their population structure and admixture, and to estimate their relatedness to several neighboring breeds. Our analyses included 142 goats belonging to 5 local breeds genotyped with the Illumina 50K BeadChip and 618 previously genotyped animals representing 15 goat breeds from Austria and Switzerland (all analyses based on 46,862 autosomal SNPs and 760 animals). In general, the conservation status of the Czech and Slovak local goat breeds was satisfactory, with the exception of the Brown Shorthair goat, as the analyzed parameters (heterozygosity, haplotype richness, ROH-based inbreeding and effective population size) were mostly above the median of 20 breeds. However, for all 5 Czech and Slovakian breeds, an examination of historical effective population size indicated a substantial decline about 8 to 22 generations ago. In addition, our study revealed that the Czech and Slovakian breeds are not fully consolidated; for instance, White Shorthair and Brown Shorthair were not clearly distinguishable. Considerable admixture, especially in Czech Landrace (effective number of parental clusters equal to 4.2), and low but numerous migration rates from other Austrian and Swiss breeds were found. These results provide valuable insights for future breeding programs and genetic diversity management of local Czech and Slovak goat breeds.

225 Genomic diversity of Katahdin sheep and impacts on genomic prediction

Abstract In the late 1950s, Katahdin hair sheep were developed as a composite breed of medium size and moderate prolificacy, with potential to express resistance to gastrointestinal nematodes. With its increasing popularity and the recent adoption of genomic prediction in the Katahdin breeding program, evaluating the genetic diversity in this breed is necessary. Prediction accuracies rely on the strength of genetic relationships. That strength often increases with selection using genomically-enhanced estimated breeding values; however, it carries the risk of decreasing diversity. We aim to characterize the genetic diversity present in the breed and the subsequent impact on the accuracies of genomic predictions. Genotypes on Katahdin sheep from member flocks in the National Sheep Improvement Program were used. Data from two medium density 50k bead chips and one high density 600k bead chip were merged and limited to shared autosomal single nucleotide polymorphisms (SNP). After quality control, there were 9,705 animals and 31,984 SNP remaining. Only for analyses of inbreeding and heterozygosity, linkage disequilibrium (LD) pruning was performed; variants with an LD score exceeding 0.8 were removed with 29,904 SNP remaining. To determine the extent of population structure, principal component (PC) analysis was conducted with PC one and PC two explaining 4.9% and 3.8% of the variation in the population, respectively. When examining subpopulations, a single ancestral population explained 99.9% of the genetic variation among animals. When clustered by identity-by-state, all animals were placed in a single cluster. Inbreeding coefficients were estimated with four methods: method of moments, variance-standardized relationship minus one, excess homozygosity, and correlation between uniting gametes. Across methods, average inbreeding coefficients ranged from 1.14% to 1.20% with Pearson and Spearman correlations ranging from -0.51 to 0.91 (Table 1). Historical effective population sizes (Ne) were estimated for earlier generations, and a linear regression fit to predict more recent Ne. At the founding of the breed, historical Ne was estimated to be 310, and the current Ne was estimated to be 150. Effects of Ne on the accuracy of genomic predictions were examined for reference population sizes ranging from 1k to 25k for traits of low (0.1), moderate (0.3), and high (0.5) heritabilities. The corresponding number of effective chromosomal segments were 2NeL, where L was the length of the genome in morgans (26M). Accuracies of genomic predictions increased as the reference population size grew, with only marginal gains once the population exceeded 15k. Overall, there were no detectable genetic subpopulations in the Katahdin breed. Current levels of inbreeding were low. With a small Ne the breed can achieve high accuracy for genomic predictions by aiming for a reference population of 15k animals. Negative impacts on genetic diversity due to genomic selection are not of immediate concern.

Effect of genetic and sex effect on genomic prediction for horn development in Nellore cattle

This study aimed to evaluate the influence of phenotypic classification of horn development, animal sex effect, and non-autosomal SNP (single nucleotide polymorphism) markers on the genetic parameters and genomic prediction ability for horn development in Nellore cattle using the single-step genomic best linear unbiased prediction method. The polled phenotype was evaluated in two (presence and absence of horns), three (scurs and polled offspring from a horned parent, and the polled and horned animals), and four (absence of horn, polled born to a parent with horn, scurs, and presence of horn) phenotypic categories. A total of 12 statistical models were evaluated. The variance components were estimated using the THRGIBBS1F90 software, and a threshold animal model was used for genomic prediction analyses with the single-step genomic BLUP (ssGBLUP) procedure. Accuracy, bias, and dispersion parameters were evaluated based on the linear regression (LR) method. The highest heritability (0.84) was obtained when the polled character was evaluated as a binary trait. The lowest heritability estimates (0.44 to 0.45) for horn development were obtained when the phenotype was classified into three categories. For the same horn development classification method, the heritability estimates were similar regardless of the genomic evaluated models and fixed effects included in the model. For models considering four and three phenotypic categories for horn development, the inclusion of the sex effect as a fixed effect within the CG did not improve the accuracy, bias, and dispersion of genomic predictions for horn development. Analyzing the trait with binary expression, the highest prediction accuracy was observed when the effect of sex was not included in the CG and without the SNPs in the sex chromosomes. These models displayed the highest dispersion, pointing out the low robustness of genomic prediction. In addition, models that use less than four categories to classify the horn development phenotype, with no discrimination between polled and homozygous polled displayed lower prediction ability. The inclusion of non-autosomal SNPs in the analyses for the models considering four phenotypic categories leads to an improvement in prediction accuracy in 5,26 %, bias, and dispersion reduction, 37 % and 4,55 %, respectively, compared with models that only considered autosomal SNPs. The selection using genomic information for the polled trait is feasible, and it is an alternative to obtaining polled Nellore animals. The binary coding of horn development is an unsuitable oversimplification of polled phenotype, and probably, the genetic background of horn development is more complex than previously proposed. The most adequate prediction model to evaluate the horn development in Nellore cattle was considering four phenotypic categories and including non-autosomal SNP in the analyses for genomic prediction purposes of naturally genetically polled animals. Genetic dehorning can be adopted on a large scale as a low-cost and non-invasive approach to increase the frequency of hornless animals using genomic information and mating strategies.

Gene-Environment Interactions and Gene-Gene Interactions on Two Biological Age Measures: Evidence from Taiwan Biobank Participants.

PhenoAge and BioAge are two commonly used biological age (BA) measures. The author here searched for gene-environment interactions (GxE) and gene-gene interactions (GxG) on PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 111,996 Taiwan Biobank (TWB) participants, including a discovery set of 86,536 TWB2 individuals and a replication set of 25,460 TWB1 individuals. Searching for variance quantitative trait loci (vQTLs) provides a convenient way to evaluate GxE and GxG. A total of 4 nearly independent (linkage disequilibrium measure r2 < 0.01) PhenoAgeAccel-vQTLs are identified from 5,303,039 autosomal TWB2 SNPs (p < 5E-8), whereas no vQTLs are found from BioAgeAccel. These 4 PhenoAgeAccel-vQTLs (rs35276921, rs141927875, rs10903013, and rs76038336) are further replicated by TWB1 (p < 5E-8). They are located in the OR51B5, FAM234A, and AXIN1 genes. All 4 PhenoAgeAccel-vQTLs are significantly associated with PhenoAgeAccel (p < 5E-8). A phylogenetic heat map of the GxE analyses showed that smoking exacerbated the PhenoAgeAccel-vQTLs' aging effects, while higher educational attainment attenuated the PhenoAgeAccel-vQTLs' aging effects. Body mass index, chronological age, alcohol consumption, and sex do not prominently modulate PhenoAgeAccel-vQTLs' aging effects. Based on these vQTL results, rs141927875-rs35276921 interaction (p = 4.7E-61) and rs76038336-rs10903013 interaction (p = 3.3E-116) on PhenoAgeAccel are detected.

Genome-wide single nucleotide polymorphisms reveal the genetic diversity and population structure of Creole goats from northern Peru

Goat farming constitutes a significant source of income for farmers in northern Peru. There is currently an absence of information about the genetics of Peruvian Creole goats that would enable us to understand their origins and genetic spread. The objective of this study was to estimate the genetic diversity of Creole goats from northern Peru using SNP markers. This study involved the collection of 192 male Creole goats from three key goat production geographical departments in northern Peru. These goat samples were genotyped using the GGPGoat70k SNP panel. To explore the genetic influence of other breeds on Peruvian Creole goats, our dataset was combined with previously published SNP genotypes. External data set includes multiple breeds genotypes sampled from Argentina, Brazil, Spain, and Alpine breed from Italy, France, and Switzerland. After quality control 52,832 autosomal SNPs were used to assess genetic diversity in the Peruvian goats. For the population structure analysis of the merged data 20,513 common SNPs were used. Estimations for expected heterozygosity (He), observed heterozygosity (Ho), and inbreeding coefficient (FIS) were computed for the Peruvian groups. AMOVA, principal component analysis and ADMIXTURE were conducted to evaluate the population structure in the two data sets, Peru and merged. The results revealed a considerable genetic diversity, with Ho values ranging from 0.40 to 0.41 for the Peruvian sampling groups, and inbreeding coefficient was notably low for Peruvian goat. The population structure analysis demonstrated a distinction (p < 0.05) from other breeds. These findings suggest a level of genetic differentiation of the Peruvian goat population among other breeds, although further research is needed considering samples from other Peruvian areas. We expect this study will contribute to define genetic management strategies to prevent the loss of genetic diversity in Peruvian goat populations and for upcoming advancements in this field.

Abstract LB379: HLA-DQB1*05:02: An independent genetic marker for oral cavity squamous cell carcinoma susceptibility

Abstract Environmental exposure to carcinogens causes mucosal damage in the upper aerodigestive tract, which can lead to cancers. The genetic basis of head and neck cancer is controversial. To identify susceptibility genes in head and neck cancers, we enrolled patients with early-onset disease in Taiwan. This case-control study included 54 young male patients with oral squamous cell carcinoma (OSCC) who were treated between March 1996 and December 2016, as well as 2,400 healthy controls. A single-nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OSCC. Sequencing-based typing (TBG Biotechnology Corp., Taipei, Taiwan) was used to determine the HLA-DQB1 genotype in another cohort of 147 OSCC patients. We analyzed the allele frequencies of 664,994 autosomal SNPs in the 54 OSCC cases. In a genome-wide association analysis, four SNPs within loci on chromosomes 6, 7, 9, and 12 were significantly different between OSCC patients and controls (corrected P &amp;lt; 1.0 × 10−6). HLA-DQB1 was closest to rs28451423 on chromosome 6. HLA-DQB1*05:02 in OSCC (18.5%) was significantly different from normal population (7.0%) (P = 0.009). The influence of disease onset was independently significant after adjusting cigarette smoking, alcohol drinking and areca-quid chewing (P = 0.015, OR: 3.922, 95% confidence interval: 1.311 - 11.734). Furthermore, HLA-DQB1*05:02 was associated with early-onset OSCC (P = 0.004). HLA-DQB1*05:02 is associated with OSCC independent of environmental exposures. HLA-DQB1*05:02 is also related with early onset of OSCC. It provides evidence of a genetic basis for OSCC. Citation Format: Shiang-Fu Huang, Huei-Tzu Chien, Chi-Kuan Young, Yun-Shien Lee, Chun-Ta Liao, Kai-Lun Cho, Ching-Han Chen. HLA-DQB1*05:02: An independent genetic marker for oral cavity squamous cell carcinoma susceptibility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB379.

Genetic architecture of inbreeding depression may explain its persistence in a population of wild red deer.

Inbreeding depression is of major concern in declining populations, but relatively little is known about its genetic architecture in wild populations, such as the degree to which it is composed of large or small effect loci and their distribution throughout the genome. Here, we combine fitness and genomic data from a wild population of red deer to investigate the genomic distribution of inbreeding effects. Based on the runs of homozygosity (ROH)-based inbreeding coefficient, FROH, we use chromosome-specific inbreeding coefficients (FROHChr) to explore whether the effect of inbreeding varies between chromosomes. Under the assumption that within an individual the probability of being identical-by-descent is equal across all chromosomes, we used a multi-membership model to estimate the deviation of FROHChr from the average inbreeding effect. This novel approach ensures effect sizes are not overestimated whilst maximising the power of our available dataset of >3000 individuals genotyped on >35,000 autosomal SNPs. We find that most chromosomes confer a minor reduction in fitness-related traits, which when these effects are summed, results in the observed inbreeding depression in birth weight, survival and lifetime breeding success. However, no chromosomes had a significant detrimental effect compared to the overall effect of inbreeding, indicating no major effect loci. We conclude that in this population, inbreeding depression is likely the result of multiple mildly or moderately deleterious mutations spread across all chromosomes, which are difficult to detect with statistical confidence. Such mutations will be inefficiently purged, which may explain the persistence of inbreeding depression in this population.