Population Allele Frequencies Research Articles

Tools for Evolutionary and Genetic Analysis (TEGA): A new platform for the management of molecular and environmental data.

Population genetics studies the distributions and changes in population allele frequencies in response to processes, such as mutation, natural selection, gene flow, and genetic drift. Researchers daily manage genetic, biological, and environmental data of the samples, storing them in text files or spreadsheets, which makes it difficult to maintain consistency and traceability. Here we present TEGA, a WEB-based stand-alone software developed for the easy analysis and management of population genetics data. It was designed to: 1) facilitate data management, 2) provide a way to execute the analysis procedures, and 3) supply a means to publish data, procedures, and results. TEGA is distributed under the GNU AGPL v3 license. The documentation, source code, and screenshots are available at https://github.com/darioelias/TEGA. In addition, we present Rabid Fish, the first implementation of TEGA in the Genetics Labortory of the Faculty of Humanities and Sciences at the National University of the Litoral, where research focuses on population genetics studies applied to non-model organisms.

ABO, Rh, and kell blood group antigen frequencies in blood donors at the tertiary care hospital of Northwestern India.

BACKGROUND:This study was performed to provide information on frequencies of ABO, Rh & Kell antigens/alleles, phenotype in blood donors at Blood Bank, SMS hospital, Jaipur and to compare them with other races.METHODOLOGY:This study was conducted on blood donors from April 2016 to March 2017 using a fully automated system for ABO,Rh & Kell typing of blood cells. D, C, c, E, e & K antigens were typed using monoclonal antisera from Immucor The data were collected and calculations done to determine the antigen/allele, phenotype. The chi square test 3 degree of freedom with P < 0.001 (S) was used for comparisons between the results of our study and those of other studies.RESULTS:A total of 8067 donors were included in this study. Maximum donors was of B blood group (39.4%) of age 18-25(35.5%) with 60-69kg weight (65%). The most common Rh antigen found was e(99.3%) followed by D (93.8%), C (85.4%), c (60.1%), E (17.5%). R1r (DCCee) was the most common phenotype in our study (39.5%). Kell (K+) antigen was present in 2.7% of donors.CONCLUSION:We have determined the prevalence of Rh antigens and Rh phenotypes in blood donor at our hospital and derived the allele frequencies in the same population.

The Apolipoprotein Allele and Sensorineural Hearing Loss in Older Community-Dwelling Adults in Australia.

Previous research has investigated whether the apolipoprotein E (APOE) ε4 allele, which is associated with an increased risk of cognitive decline, is also associated with hearing loss in older people. Results of the very limited research to date are conflicting, and sample sizes for all but one study were small. The present study aimed to investigate whether there is an association between the APOE ε4 allele and hearing loss in a large, population-based sample of community-dwelling older adults. Cross-sectional audiometric data on hearing levels and APOE genotypes for 2006 participants (aged 55 to 85 years) of the Hunter Community Study were analyzed using multiple linear regression to examine the association between APOE ε4 carrier status and the 4-frequency pure-tone average (0.5 to 4 kHz) in the better hearing ear, and also across individual frequencies in the better ear. Observed and expected APOE allele frequency distributions did not differ significantly overall from established general population allele frequency distributions. Unadjusted modeling using better ear pure-tone average showed a statistically significant association between APOE ε4 allele status (0, 1, 2 copies) and reduced hearing loss, but when the model was adjusted for age, this was no longer statistically significant. Across individual hearing frequencies, unadjusted regression modeling showed APOE ε4 status was significantly associated with a reduction in mean hearing thresholds at 1 and 2 kHz, but again this effect was no longer statistically significant after adjusting for age. The results of this study did not provide any evidence of a statistically significant association between APOE ε4 allele status and hearing loss for older adults. Further investigation of the effect of homozygous carrier status on hearing thresholds is required.

HLA and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1*08:04 and HLA-DRB1*11:02 alleles were associated with overall SSc risk, and the HLA-DRB1*08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1*13:01 and HLA-DRB1*07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1*13:01 allele with the ATA+ subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1*13:01 allele frequency in multiple populations was observed (r = 0.98, P = 3 × 10-6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA α/β allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc.

MGeND: an integrated database for Japanese clinical and genomic information

To promote the implementation of genomic medicine, we developed an integrated database, the Medical Genomics Japan Variant Database (MGeND). In its first release, MGeND provides data regarding genomic variations in Japanese individuals, collected by research groups in five disease fields. These variations consist of curated SNV/INDEL variants and susceptibility variants for diseases established by genome-wide association study analysis. Furthermore, we recorded the frequencies of HLA alleles in infectious disease populations.

Genetic variants in DGAT1 cause diverse clinical presentations of malnutrition through a specific molecular mechanism

BackgroundDGAT1, a gene encoding a protein involved in lipid metabolism, has been recently implicated in causing a rare nutritional and digestive disease presenting as Congenital Diarrheal Disorder (CDD). Genetic causes of malnutrition can be classified as metabolic disorders, caused by loss of a specific enzyme's function. However, disease driven by genetic variants in lipid metabolism genes is not well understood, and additional information is needed to better understand these effects. MethodsWe gathered a multi-institutional cohort of undiagnosed patients with a constellation of phenotypes presenting as malnutrition and metal ion dysregulation. Clinical Whole Exome Sequencing (WES) was performed on four patients and their unaffected parents. We prioritized genetic variants based on multiple criteria including population allele frequency and presumed inheritance pattern, and identified a candidate gene. Computational modeling was used to investigate if the altered amino acids are likely to result in a dysfunctional enzyme. ResultsWe identified a multi-institutional cohort of patients presenting with malnutrition-like symptoms and likely pathogenic genomic variants within DGAT1. Multiple approaches were used to profile the effect these variants have on protein structure and function. Laboratory and nutritional intervention studies showed rapid and robust patient responses. ConclusionsThis report adds on to the database for existing mutations known within DGAT1, a gene recently implicated with CDD, and also expands its clinical spectrum. Identification of these DGAT1 mutations by WES has allowed for changes in the patients’ nutritional rehabilitation, reversed growth failure and enabled them to be weaned off of total parenteral nutrition (TPN).

Melanocortin 4 Receptor Gene Sequence Analyses in Diverse Populations.

Background: Melanocortin 4 receptor (MC4R) is a G-protein-coupled receptor involved in appetite regulation. Mutations in the MC4R gene are the most common cause of monogenic obesity. More than 200 sequence variants in the MC4R gene have been associated with obesity, although the vast majority of these data have been obtained from populations of European ancestry. The prevalence and mutation profile of MC4R is thus poorly characterized in other ancestries/ethnicities. Materials and Methods: We surveyed the allele frequencies of the MC4R variants of multiple racial/ethnic populations represented in the Genome Aggregation Database (gnomAD) and sequenced the MC4R gene in a diverse population of 60 individuals with extreme obesity. Results: Allele frequencies were similar for most classes of variants except for a higher rate of synonymous substitutions in the African gnomAD population. We also identified two apparently novel MC4R variants and two variants with much higher allele frequencies in African populations whose functional impacts are not yet known. Conclusion: These results highlight the need for characterizing MC4R variants in diverse populations with extreme obesity.

Incidence of Germline ATM Variants in a Consecutive Clinical Cohort of CLL Patients

Incidence of Germline ATM Variants in a Consecutive Clinical Cohort of CLL Patients

Germline Gene Aberrations Are Common in High-Risk Adult and Pediatric Acute Lymphoblastic Leukemia Patients

Personalized medicine involves a comprehensive analysis of factors affecting a disease. Family history is an important but not a definitive indicator of inherited predisposition to malignancy and thus studying the germline gene aberrations alongside somatic variants is warranted. The significance of germline predisposition has been increasingly recognized in acute myeloid leukemia and is noted in the latest WHO classification.1,2,3Despite the recent progress in acute lymphoblastic leukemia (ALL) therapies, many adult patients with ALL still do poorly and there is a need for new biomarkers and therapy targets. The aim of our study was to identify and determine the frequency of germline mutations in known ALL genes, to discover new genes associated with ALL predisposition, and to compare the germline genetic background and respective consequences of pediatric and adult high-risk ALL. We examined exome sequencing data from biobanked samples of adult (50) and pediatric (68) patients with high-risk ALL (Finnish Hematological Registry and Biobank - FHRB, and clinical repositories). First, a candidate-gene analysis consisted of 92 genes previously associated with germline predisposition to ALL or syndromes predisposing to ALL. Variants with minor allele frequency of &amp;lt;0.01 in the Genome Aggregation Database were considered. Missense variants were considered significant if ≥2/3 algorithms (CADD, DANN, Revel) classified it as pathogenic. We also reviewed literature, public databases and the American College of Medical Genetics classification (ACMG) in filtering the variants. Clinical characteristics of the patients were retrieved from hospital records and the Finnish Hematological Registry. Second, an unbiased approach was applied to find novel genes predisposing to ALL by checking pathogenic variants in the same gene in at least two (adult/pediatric) patients and filtering by gene ontologies DNA repair, cell cycle, and lymphocyte differentiation; and by COSMIC cancer census genes. In both analyses, only statistically significantly more common variants in our series compared to normal population were included. We also conducted a mutational signature analysis on the samples. Our analysis (Table 1) demonstrates that 8% of adult and 10% pediatric study patients carried a pathogenic or likely pathogenic mutation in their germline in known ALL predisposing genes. All these mutations were at least 30-fold more frequent in our study series compared with allele frequencies in the normal population (p&amp;lt;0.05). Four pediatric patients were identified to suffer from undiagnosed syndromes, which predispose to ALL (Li-Fraumeni and Noonan syndromes). We also found recurring aberrations in new genes with biological relevance to ALL, such as MUTYH and IL21R, potentially associating with ALL predisposition. Final results of the mutational signature analyses are pending. In conclusion, our results emphasize that germline predisposition is not rare among high-risk ALL patients. In addition to pediatric ALL patients, we show contributing germline variants also in adult patients. At least 20% of the adult ALL patients are transplanted and a potential germline basis of the disease should be considered when choosing the donor. Our analysis also reveals new information on the biology of high-risk ALL and may contribute to the future studies seeking for therapy options in this challenging patient category. Despite the anxiety that acknowledging inheritable factors may cause in patients, families, and caretakers, we encourage clinicians to integrate carefully interpreted germline data into patient care.

Immune Sculpting of Clonal Hematopoiesis in Advanced and Metastatic Solid Tumors

Clonal hematopoiesis (CH) is described as the phenomenon where hematopoietic cells acquire advantageous somatic mutations that result in a dominant subclonal population. These subclones are linked to various adverse outcomes such as elevated risk of hematologic malignancies and cardiovascular disease. Few studies, however, address the presence and role of CH in clinically-relevant advanced and metastatic solid tumors or how progression of CH is altered via immune selection. Here, we identified and quantified CH mutations in 883 patients with 64 different advanced solid cancer subtypes. The age of patients ranged from 1 to 96, with the average age being 66.7 years. In this cohort, whole exome sequencing (WES) of tumor and matched peripheral blood was conducted through the Englander Institute of Precision Medicine. CH was identified through mutations in the peripheral blood that were absent in the tumor. Probable SNPs were filtered using population allele frequency data from the ExAC database. Tumor mutation burden (TMB) and microsatellite instability (MSI) scores were calculated for each patient. MHC Class I alleles for HLA types A, B, C were inferred for each patient based on WES. CH was identified in 12% of patients and 19 different solid advanced and metastatic cancer subtypes and was associated with increased age (P &lt; 0.001). Cancer subtypes with the highest frequency of CH mutations were urothelial carcinoma, glioblastoma, adenocarcinoma, and transitional cell (urothelial) carcinoma. The most commonly mutated genes were DNMT3A, TET2, ASXL1, and BCOR1. We restricted further analysis to the most common CH genes: DNMT3A, TET2, and ASXL1. 60% of patients with CH had only one mutation, 13% had two mutations, and 4% had 3 or more mutations. When adjusting for covariates including tumor subtype and age, the presence of CH was suggestive of elevated MSI scores (P &lt; 0.1) but did not impact TMB. We next sought to determine if MHC class impacted susceptibility to the emergence of CH. Fisher's exact test was used to identify associations between HLA alleles and the presence of CH. We identified MHC alleles conferring hyper-susceptibility to CH development by as much as 8-fold (OR 8.0, 95% C.I. 2.1 - 39.1, P &lt; 0.001). We further identified 52 probable protective alleles. These data suggest that certain HLA alleles are significantly more permissive to CH development, while others may be protective against CH. Overall, our study is the first to systematically evaluate and suggest that patient-specific hyper-susceptibility HLA alleles impact evolutionary processes that underlie clonal sculpting leading to the emergence of CH. The presence of CH may also impact the evolution of co-occurring solid tumors, a hypothesis requiring further evaluation. This study indicates that MHC alleles and thus personal genetics place immunity-driven selective pressure for the emergence of CH, supporting the role of inherited determinants of CH. Disclosures No relevant conflicts of interest to declare.

The HLA-G 14 bp allele frequency in different populations: A global meta-analysis

HLA-G gene encodes a non-classical molecule of major histocompatibility complex with important immunomodulatory properties, being expressed, primarily by cytotrophoblasts during pregnancy, or in pathological conditions (autoimmune diseases, cancer, transplants and viral infections). The insertion of 14 bp in HLA-G 3′UTR region has been related to reduced mRNA levels, consequently affecting the protein levels. Due to its importance for gene expression and in the context of several physiopathologic conditions, we assessed, by meta-analysis, the global distribution of the HLA-G 14 bp insertion allele frequency. We searched genetic association studies, published between 1997 and 2018, indexed in the PubMed, Science Direct and Google Scholar databases, using the descriptor: “HLA-G 14 bp”. All studies that presented allele counts in the healthy controls were included. We analyzed 20,755 individuals from 112 different populations of Africa, Asia, American and Europe. The global allelic frequency of HLA-G 14 bp insertion was 0.42 (95%CI = 0.41–0.44). When stratifying according to the continents, we observed the highest allelic frequency in the African continent (0.51) and the lowest in the European continent (0.41). Our meta-analysis demonstrates that HLA-G 14 bp insertion allele have a similar distribution around the world, indicating a possible action of balancing selection.

Novel single nucleotide polymorphisms in the heat shock protein 70.1 gene in South African Nguni crossbred cattle.

High environmental temperatures are one of the main causes of reduced productivity and reproduction in livestock. In an endeavour to counteract the effects of high temperature, a special class of proteins known as heat shock proteins function to alleviate heat stress in the cells. In this study, two regions (3'- and 5'-UTR) of the heat shock protein 70.1 (HSP70.1) gene were studied in Nguni crossbred cattle. Subsequently, the population genetic structure was elucidated. The 5'-UTR contained the most polymorphisms with 46 and 67 SNPs, while the 3'-UTR contained 7 and 16 SNPs in the Umzimkulu and Port Shepstone populations, respectively. The T64G polymorphism had the greatest frequency of all returned SNPs in the 3'-UTR; it was fixed for the Umzimkulu population (allele frequency = 1.00) and was nearing fixation in the Port Shepstone population (allele frequency = 0.979). In the 5'-UTR, the cytosine insertion at position 1110 was fixed for both populations. These polymorphisms are presumed to play a major role in the high thermotolerance exhibited in Nguni crossbred cattle. Partitioning of genetic variation displayed that the majority of the variation (96%) was within populations, whereas only 4% of the variation was due to population genetic differentiation. A total of 22 haplotypes defined the 5'-UTR while the 3'-UTR contained 4. In conclusion, this study demonstrated that Nguni crossbred cattle in the KwaZulu-Natal province of South Africa are clustered into two genetic groups based on the HSP70.1 gene. The findings of this research will provide future directions on the identification of important SNPs within the HSP70.1 gene in South African indigenous cattle because this is one of the first of such studies.

Single step strategy for estimating unknown STR allele frequencies in a population

Constant growth of forensic DNA databases requires new STR markers to be developed, tested and validated. Aiming to simplify the process of obtaining allele frequency distributions of new STR loci included in new megaplexes, a single step protocol was developed. This goal was achieved by pooling samples of genetically unrelated donors, previously genotyped (n = 99), containing the same amount of DNA (total DNA = 4.5 ng/ul) as measured by fluorometry. Suitability of the method was tested by amplifying commercial kits: GlobalFiler (GF), Verifiler Express (VFE) and Y-filer plus (YFP). Allele peak heights was used to estimate allele frequency and compared with the actual frequency calculated by counting method of the individual pooled samples. The multinomial goodness of fit test was performed for testing statistical differences.In case of VFE, 4.5 ng was the DNA amount that could best estimate the allele frequency distribution; 1 ng for GF and YFP. For simple, complex and compound makers, the highest allele frequencies were correctly estimated (p > 0.05) but in some cases, it was not able to detect alleles in very low frequencies, 2/198 or below, either with VFE or GF.In case of D12S391, either for VFE and GF, some microvariants with frequency of 2, 3 or 5/198 were not assigned although they were present in the profiles, probably due to POP7 resolution. In case of YFP, some alleles were not detected at DYS385.Nevertheless, with some limitations, the proposed strategy proved to be fast and efficient for major allele frequency estimation. This simple approach generates an empirical distribution that allows for the estimation of population allele frequencies in a single step assay.

Future Preventive Gene Therapy of Polygenic Diseases from a Population Genetics Perspective.

With the accumulation of scientific knowledge of the genetic causes of common diseases and continuous advancement of gene-editing technologies, gene therapies to prevent polygenic diseases may soon become possible. This study endeavored to assess population genetics consequences of such therapies. Computer simulations were used to evaluate the heterogeneity in causal alleles for polygenic diseases that could exist among geographically distinct populations. The results show that although heterogeneity would not be easily detectable by epidemiological studies following population admixture, even significant heterogeneity would not impede the outcomes of preventive gene therapies. Preventive gene therapies designed to correct causal alleles to a naturally-occurring neutral state of nucleotides would lower the prevalence of polygenic early- to middle-age-onset diseases in proportion to the decreased population relative risk attributable to the edited alleles. The outcome would manifest differently for late-onset diseases, for which the therapies would result in a delayed disease onset and decreased lifetime risk; however, the lifetime risk would increase again with prolonging population life expectancy, which is a likely consequence of such therapies. If the preventive heritable gene therapies were to be applied on a large scale, the decreasing frequency of risk alleles in populations would reduce the disease risk or delay the age of onset, even with a fraction of the population receiving such therapies. With ongoing population admixture, all groups would benefit over generations.

Disaster victim identification by kinship analysis: the Lampedusa October 3rd, 2013 shipwreck

On October 3rd, 2013 a boat carrying more than 500 migrants coming mostly from the Horn of Africa (Eritrea, Somalia, Ethiopia) sank near Lampedusa, a small Italian Island in the middle of the Mediterranean Sea. The recovered bodies were examined by a forensic team, and post mortem data (anthropological and odontological records, and DNA) were collected for identification. Genetic profiles based on 16 autosomal STRs were acquired from both victims and putative relatives recruited following an international call. The final genetic database included 363 victims and 43 reference persons from 36 independent families recruited until mid-2017, who were missing 35 first-degree and 6 second-degree relatives. A pairwise blind search approach was used to identify familial relationships within the victims and between victims and putative relatives. Two statistics were calculated, the Identity by State (IBS) and the Identity by Descent (IBD), the latter by using the DVI module of the FAMILIAS3 software to compute LRs and posterior probabilities. The putative identifications were confirmed in pedigree analysis using the information provided by the relatives. In selected cases, additional autosomal and lineage (Y-chromosome and mtDNA) markers were typed. Some critical points were highlighted: the lack for accurate allele and haplotype frequencies in African populations, especially for the lineage markers, and the need for a shared approach to the biostatistical interpretation of the results in DVI. In the end, 29 first-degree (parent-child and full sibs) out of 35 missing (83%), and 3 out of 6 of second-degree relatives (50%) showed a high statistical confidence for a positive identification. This study represents the first attempt to systematically deal with the genetic identification of African migrants who died in the Mediterranean Sea. The methodological and statistical approach used in this study was proved to be reliable and appropriate for future genetic identifications in other similar mass disasters.

808P - Investigation on gastric cancer susceptibility genes in Chinese early-onset diffuse gastric cancer

BackgroundHereditary diffuse gastric cancer (HDGC) is closely related to germline mutation of CDH1. In addition, potential pathogenic germline variants in other candidate genes were detected in FGC and HDGC families. However, comprehensive genetic profile of HDGC predisposing gene variants in Chinese Familial gastric cancer (FGC) and HDGC patients are yet to be elucidated. MethodsWe collected peripheral blood from 28 early-onset DGC patients and from a first degree relative DGC patient who was diagnosed at age of 50. All 29 patients fulfilled IGCLC 2015 criteria for HDGC clinical diagnosis and genetic testing. Genomic DNA was extracted from peripheral blood followed by Whole Exome Sequencing (WES) with average sequencing depth of at least 100X. Gastricancer predisposing SNV and Indel candidates were filtered based on population allele frequencies in public nucleotide polymorphism databases and corresponding functional impact was predicted by in silico tools. ResultsAmong previously reported gastric cancer susceptibility genes, CDH1, BRCA2, MAP3K6 expressed the most predisposing SNV and Indel candidates. In addition, a novel splice-site variant, c.2165-1G>A, in CDH1 was detected in a Chinese early-onset HDGC patient who developed ovarian metastasis. Moreover, BCR gene exhibited as the most prevalent gastric cancer predisposing gene with filtered variants primarily enriched in RhoGAP domain. Pathway enrichment analysis showed that the top three predisposing variant candidates were enriched in the following signalling pathway: ECM-receptor interaction (P-Value: 0.001), focal adhesion (P-Value: 0.02) and protein digestion and absorption (P-Value: 0.002). ConclusionsThis study suggested that CDH1, BRCA2, MAP3K6 may act as potential gastric cancer susceptibility genes in Chinese early-onset HDGC patients. Further study may be required to investigate the functional role of BCR abnormality, especially in its RhoGAP domain, in the tumorigenesis of gastric cancer. Moreover, to further investigate molecular mechanisms of early-onset gastric cancer, one may consider genes involved in three signalling pathways: ECM-receptor interaction, focal adhesion and protein digestion and absorption. Legal entity responsible for the studyPeking University Cancer Hospital. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations

Each human genome carries tens of thousands of coding variants. The extent to which this variation is functional and the mechanisms by which they exert their influence remains largely unexplored. To address this gap, we leverage the ExAC database of 60,706 human exomes to investigate experimentally the impact of 2009 missense single nucleotide variants (SNVs) across 2185 protein-protein interactions, generating interaction profiles for 4797 SNV-interaction pairs, of which 421 SNVs segregate at > 1% allele frequency in human populations. We find that interaction-disruptive SNVs are prevalent at both rare and common allele frequencies. Furthermore, these results suggest that 10.5% of missense variants carried per individual are disruptive, a higher proportion than previously reported; this indicates that each individual’s genetic makeup may be significantly more complex than expected. Finally, we demonstrate that candidate disease-associated mutations can be identified through shared interaction perturbations between variants of interest and known disease mutations.

Autozygosity and Genetic Differentiation of Landrace and Large White Pigs as Revealed by the Genetic Analyses of Crossbreds.

Genomic information from crossbreds is routinely generated for genomic evaluations. The objective of this study is to investigate autozygosity and genetic differentiation in Landrace by Large-White breeds by using the genotypic information of SNP arrays in 1,173 crossbreds. A maximum likelihood approach was developed to estimate the probability of autozygosity (FL). Regions of differentiation between breeds were investigated using FST and the difference in allele frequencies between the two parental breeds (릌Δ) at each single-nucleotide polymorphism (SNP) position. A maximum likelihood approach was proposed to estimate allele frequencies in the parental populations. The average length of runs of homozygosity (ROH) across the genome was 3.91, 2.3, and 0.7 Mb for segments with at least 25, 15, and 5 SNPs, respectively. Average age to coalesce was 46, 414, and 388 years for segments with at least 25, 15, and 5 SNPs, respectively. The probability of autozygosity was not uniform along the crossbred genome, being higher at the center for most chromosomes. The correlation between autozygosity and distance to the closest telomere was positive and significant in most chromosomes, which could be attributed to the higher recombination rate near telomeres. We also report a relatively high negative correlation between probability of recombination (from a published map) and probability of autozygosity. It supports that structural characteristics of the chromosomes related to recombination rate determine autozygosity at each chromosomal position of the pig genome. The average is Δ across the genome was 0.17 (SD = 0.16). After testing for differences in allele frequencies between the parental breeds, there were 4,184 SNPs with a likelihood ratio test, LRT ≥ 32.02. The average FST across the genome was 0.038 (SD = 0.059). There were 2,949 SNPs with FST > 0.125. The correlation between estimates of FL and estimates of FST across the genome was -0.10 (SE = 0.006). Analysis of the gene content of the genomic regions with the 2000 SNPs with highest LRT for FL and high FST showed overrepresentation of genes with a regulatory function. Genes with biological functions associated with production, such as tissue development, anatomical structure, and animal organ development, were also overrepresented in regions with a high FST.

Population genomics reveals possible genetic evidence for parallel evolution of Sebastiscus marmoratus in the northwestern Pacific Ocean.

Understanding patterns of population diversity and structuring among marine populations is of great importance for evolutionary biology, and can also directly inform fisheries management and conservation. In this study, genotyping-by-sequencing was used to assess population genetic diversity and connectivity of Sebastiscus marmoratus. Based on 130 individuals sampled from 10 locations in the northwestern Pacific Ocean, we identified and genotyped 17 653 single-nucleotide polymorphisms. The patterns of genetic diversity and population differentiation suggested that the Okinawa Trough might be the ancestral centre of S. marmoratus after the Last Glacial Maximum. A shallow genetic structure was observed among sampled populations based on the implemented structuring approaches. Surprisingly, we detected genetic homogeneity in two population pairs (i.e. Xiamen–Niigata and Zhuhai–Iki Island), in which populations have large geographical and latitudinal intervals. Population structure and allele frequency distribution based on outlier loci also mirrored the observed genetic homogeneity in the above-mentioned population pairs. Integrated with biological, environmental and genomic data, our results provide possible genetic evidence for parallel evolution. Our study also provides new perspectives on the population structure of S. marmoratus, which could have important implications for sound management and conservation of this fishery species.

CRUMBLER: A tool for the prediction of ancestry in cattle.

In many beef and some dairy production systems, crossbreeding is used to take advantage of breed complementarity and heterosis. Admixed animals are frequently identified by their coat color and body conformation phenotypes, however, without pedigree information it is not possible to identify the expected breed composition of an admixed animal and in the presence of selection, the actual composition may differ from expectation. As the roles of DNA and genotype data become more pervasive in animal agriculture, a systematic method for estimating the breed composition (the proportions of an animal’s genome originating from ancestral pure breeds) has utility for a variety of downstream analyses including the estimation of genomic breeding values for crossbred animals, the estimation of quantitative trait locus effects, and heterosis and heterosis retention in advanced generation composite animals. Currently, there is no automated or semi-automated ancestry estimation platform for cattle and the objective of this study was to evaluate the utility of extant public software for ancestry estimation and determine the effects of reference population size and composition and number of utilized single nucleotide polymorphism loci on ancestry estimation. We also sought to develop an analysis pipeline that would simplify this process for members of the livestock genomics research community. We developed and tested a tool, “CRUMBLER”, to estimate the global ancestry of cattle using ADMIXTURE and SNPweights based on a defined reference panel. CRUMBLER, was developed and evaluated in cattle, but is a species agnostic pipeline that facilitates the streamlined estimation of breed composition for individuals with potentially complex ancestries using publicly available global ancestry software and a specified reference population SNP dataset. We developed the reference panel from a large cattle genotype data set and breed association pedigree information using iterative analyses to identify purebred individuals that were representative of each breed. We also evaluated the numbers of markers necessary for breed composition estimation and simulated genotypes for advanced generation composite animals to evaluate the precision of the developed tool. The developed CRUMBLER pipeline extracts a specified subset of genotypes that is common to all current commercially available genotyping platforms, processes these into the file formats required for the analysis software, and predicts admixture proportions using the specified reference population allele frequencies.