Sardinians Genetic Background Explained by Runs of Homozygosity and Genomic Regions under Positive Selection

: Detection of selection footprints provides insight into the evolution process and the underlying mechanisms controlling the phenotypic diversity of traits that have been exposed to selection. Selection focused on certain characters, mapping certain genomic regions often shows a loss of genetic diversity with an increased level of homozygosity. Therefore, the runs of homozygosity (ROHs), homozygosity by descent (HBD), and effective population size (Ne) are effective tools for exploring the genetic diversity, understanding the demographic history, foretelling the signature of directional selection, and improving the breeding strategies to use and conserve genetic resources. We characterized the ROH, HBD, Ne, and signature of selection of six Chinese goat populations using single nucleotide polymorphism (SNP) 50K Illumina beadchips. Our results show an inverse relationship between the length and frequency of ROH. A long ROH length, higher level of inbreeding, long HBD segment, and smaller Ne in Guangfeng (GF) goats suggested intensive selection pressure and recent inbreeding in this breed. We identified six reproduction-related genes within the genomic regions with a high ROH frequency, of which two genes overlapped with a putative selection signature. The estimated pair-wise genetic differentiation (FST) among the populations is 9.60% and the inter- and intra-population molecular variations are 9.68% and 89.6%, respectively, indicating low to moderate genetic differentiation. Our selection signatures analysis revealed 54 loci harboring 86 putative candidate genes, with a strong signature of selection. Further analysis showed that several candidate genes, including MARF1, SYCP2, TMEM200C, SF1, ADCY1, and BMP5, are involved in goat fecundity. We identified 11 candidate genes by using cross-population extended haplotype homozygosity (XP-EHH) estimates, of which MARF1 and SF1 are under strong positive selection, as they are differentiated in high and low reproduction groups according to the three approaches used. Gene ontology enrichment analysis revealed that different biological pathways could be involved in the variation of fecundity in female goats. This study provides a new insight into the ROHs patterns for maintenance of within breed diversity and suggests a role of positive selection for genetic variation influencing fecundity in Chinese goat.

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Runs of homozygosity reveal signatures of positive selection for reproduction traits in breed and non-breed horses

BMC Genomics ◽

10.1186/s12864-015-1977-3 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 69

Author(s):

Julia Metzger ◽

Matthias Karwath ◽

Raul Tonda ◽

Sergi Beltran ◽

Lídia Águeda ◽

...

Keyword(s):

Positive Selection ◽

Runs Of Homozygosity ◽

Reproduction Traits ◽

Selection For

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Identity-by-descent analyses for measuring population dynamics and selection in recombining pathogens

10.1101/088039 ◽

2016 ◽

Cited By ~ 3

Author(s):

Lyndal Henden ◽

Stuart Lee ◽

Ivo Mueller ◽

Alyssa Barry ◽

Melanie Bahlo

Keyword(s):

Drug Resistance ◽

Positive Selection ◽

Whole Genome Sequencing Data ◽

Population Bottlenecks ◽

Human Pathogens ◽

Sequencing Data ◽

Antimalarial Drug Resistance ◽

Genomic Regions ◽

Genomic Locations ◽

Critical Regions

AbstractIdentification of genomic regions that are identical by descent (IBD) has proven useful for human genetic studies where analyses have led to the discovery of familial relatedness and fine-mapping of disease critical regions. Unfortunately however, IBD analyses have been underutilized inanalysis of other organisms, including human pathogens. This is in part due to the lack of statistical methodologies for non-diploid genomes in addition to the added complexity of multiclonal infections. As such, we have developed an IBD methodology, called isoRelate, for analysis of haploid recombining microorganisms in the presence of multiclonal infections. Using the inferred IBD status at genomic locations, we have also developed a novel statistic for identifying loci under positive selection and propose relatedness networks as a means of exploring shared haplotypes within populations. We evaluate the performance of our methodologies for detecting IBD and selection, including comparisons with existing tools, then perform an exploratory analysis of whole genome sequencing data from a global Plasmodium falciparum dataset of more than 2500 genomes. This analysis identifies Southeast Asia as havingmany highly related isolates, possibly as a result of both reduced transmission from intensified control efforts and population bottlenecks following the emergence of antimalarial drug resistance. Many signals of selection are also identified, most of which overlap genes that are known to be associated with drug resistance, in addition to two novel signals observed in multiple countries that have yet to be explored in detail. Additionally, we investigate relatedness networks over the selected loci and determine that one of these sweeps has spread between continents while the other has arisen independently in different countries. IBD analysis of microorganisms using isoRelate can be used for exploring population structure, positive selection and haplotype distributions, and will be a valuable tool for monitoring disease control and elimination efforts of many diseases.

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Genomic measures of inbreeding coefficients and genome-wide scan for runs of homozygosity islands in Iranian river buffalo, Bubalus bubalis

10.21203/rs.2.17561/v3 ◽

2020 ◽

Author(s):

Seyed Mohammad Ghoreishifar ◽

Hossein Moradi-Shahrbabak ◽

Mohammad Hossein Fallahi ◽

Ali Jalil Sarghale ◽

Mohammad Moradi-Shahrbabak ◽

...

Keyword(s):

Muscle Development ◽

Bone Development ◽

Genomic Relationship Matrix ◽

Relationship Matrix ◽

River Buffalo ◽

Runs Of Homozygosity ◽

Effective Population ◽

A Genome ◽

Genomic Inbreeding ◽

Genomic Regions

Abstract Background: Consecutive homozygous fragments of a genome inherited by offspring from a common ancestor are known as runs of homozygosity (ROH). ROH can be used to calculate genomic inbreeding and to identify genomic regions that are potentially under historical selection pressure. The dataset of our study consisted of 254 Azeri (AZ) and 115 Khuzestani (KHZ) river buffalo genotyped for ~65000 SNPs for the following two purposes: 1) to estimate and compare inbreeding calculated using ROH (FROH), excess of homozygosity (FHOM), correlation between uniting gametes (FUNI), and diagonal elements of the genomic relationship matrix (FGRM); 2) to identify frequently occurring ROH (i.e. ROH islands) for our selection signature and gene enrichment studies. Results: In this study, 9102 ROH were identified, with an average number of 21.2±13.1 and 33.2±15.9 segments per animal in AZ and KHZ breeds, respectively. On average in AZ, 4.35% (108.8±120.3 Mb), and in KHZ, 5.96% (149.1±107.7 Mb) of the genome was autozygous. The estimated inbreeding values based on FHOM, FUNI and FGRM were higher in AZ than they were in KHZ, which was in contrast to the FROH estimates. We identified 11 ROH islands (four in AZ and seven in KHZ). In the KHZ breed, the genes located in ROH islands were enriched for multiple Gene Ontology (GO) terms (P≤0.05). The genes located in ROH islands were associated with diverse biological functions and traits such as body size and muscle development (BMP2), immune response (CYP27B1), milk production and components (MARS, ADRA1A, and KCTD16), coat colour and pigmentation (PMEL and MYO1A), reproductive traits (INHBC, INHBE, STAT6 and PCNA), and bone development (SUOX). Conclusion: The calculated FROH was in line with expected higher inbreeding in KHZ than in AZ because of the smaller effective population size of KHZ. Thus, we find that FROH can be used as a robust estimate of genomic inbreeding. Further, the majority of ROH peaks were overlapped with or in close proximity to the previously reported genomic regions with signatures of selection. This tells us that it is likely that the genes in the ROH islands have been subject to artificial or natural selection.

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Runs of homozygosity analysis reveals consensus homozygous regions affecting production traits in Chinese Simmental beef cattle

BMC Genomics ◽

10.1186/s12864-021-07992-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Guoyao Zhao ◽

Yuqiang Liu ◽

Qunhao Niu ◽

Xu Zheng ◽

Tianliu Zhang ◽

...

Keyword(s):

Beef Cattle ◽

Candidate Genes ◽

Average Length ◽

Snp Array ◽

Reproductive Traits ◽

Farm Animals ◽

Production Traits ◽

Runs Of Homozygosity ◽

Exact Test ◽

Genomic Regions

Abstract Background Genomic regions with a high frequency of runs of homozygosity (ROH) are related to important traits in farm animals. We carried out a comprehensive analysis of ROH and evaluated their association with production traits using the BovineHD (770 K) SNP array in Chinese Simmental beef cattle. Results We detected a total of 116,953 homozygous segments with 2.47Gb across the genome in the studied population. The average number of ROH per individual was 99.03 and the average length was 117.29 Mb. Notably, we detected 42 regions with a frequency of more than 0.2. We obtained 17 candidate genes related to body size, meat quality, and reproductive traits. Furthermore, using Fisher’s exact test, we found 101 regions were associated with production traits by comparing high groups with low groups in terms of production traits. Of those, we identified several significant regions for production traits (P < 0.05) by association analysis, within which candidate genes including ECT2, GABRA4, and GABRB1 have been previously reported for those traits in beef cattle. Conclusions Our study explored ROH patterns and their potential associations with production traits in beef cattle. These results may help to better understand the association between production traits and genome homozygosity and offer valuable insights into managing inbreeding by designing reasonable breeding programs in farm animals.

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Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

10.1101/703439 ◽

2019 ◽

Cited By ~ 1

Author(s):

Meenu Bhati ◽

Naveen Kumar Kadri ◽

Danang Crysnanto ◽

Hubert Pausch

Keyword(s):

Whole Genome Sequencing ◽

Meat Quality ◽

Genome Sequencing ◽

Genomic Diversity ◽

Whole Genome ◽

Runs Of Homozygosity ◽

Cattle Breeds ◽

Signatures Of Selection ◽

Genomic Inbreeding ◽

Genomic Regions

AbstractBackgroundAutochthonous cattle breeds represent an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution.ResultsWe annotated 15,722,811 million SNPs and 1,580,878 million Indels including 10,738 and 2,763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive xanthinuria and albinism. The average nucleotide diversity (1.6 × 10-3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding quantified using runs of homozygosity (ROH) was relatively low (FROH=0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in more recent generations of OB cattle (FROH=0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P < 0.005) of past and ongoing selection. These selection signals were enriched for quantitative trait loci related to beef traits including meat quality, feed efficiency and body weight and pathways related to blood coagulation, nervous and sensory stimulus.ConclusionsWe provide a comprehensive overview of sequence variation in Swiss OB cattle genomes. With WGS data, we observe higher genomic diversity and less inbreeding in OB than many European mainstream cattle breeds. Footprints of selection were detected in genomic regions that are possibly relevant for meat quality and adaptation to local environmental conditions. Considering that the population size is low and genomic inbreeding increased in the past generations, the implementation and adoption of optimal mating strategies seems warranted to maintain genetic diversity in the Swiss OB cattle population.

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A distinct expression profile in the cerebellum and striatum for genes under selection within introgression deserts

10.1101/2021.03.26.437167 ◽

2021 ◽

Author(s):

Raul Buisan ◽

Juan Moriano ◽

Alejandro Andirko ◽

Cedric Boeckx

Keyword(s):

Positive Selection ◽

Evolutionary History ◽

Developmental Stages ◽

Homo Sapiens ◽

Transcriptomic Data ◽

Functional Differences ◽

History Of ◽

Genomic Regions ◽

Cerebral Neocortex

Analyses of ancient DNA from extinct hominins have provided unique insights into the complex evolutionary history of Homo sapiens, intricately related to that of the Neanderthals and the Denisovans as revealed by several instances of admixture events. These analyses have also allowed the identification of introgression deserts: genomic regions in our species that are depleted of `archaic' haplotypes. The presence of genes like FOXP2 in these deserts has been taken to be suggestive of brain-related functional differences between Homo species. Here, we seek a deeper characterization of these regions, taking into account signals of positive selection in our lineage. Analyzing publicly available transcriptomic data from the human brain at different developmental stages, we found that structures outside the cerebral neocortex, and especially the cerebellum and the striatum at prenatal stages, show the most divergent transcriptomic profiles when considering genes under positive selection within introgression deserts.

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Revisiting the Notion of Deleterious Sweeps

Genetics ◽

10.1093/genetics/iyab094 ◽

2021 ◽

Author(s):

Parul Johri ◽

Brian Charlesworth ◽

Emma K Howell ◽

Michael Lynch ◽

Jeffrey D Jensen

Keyword(s):

Positive Selection ◽

Selective Sweep ◽

Significant Proportion ◽

Functional Genomic ◽

Deleterious Mutations ◽

Beneficial Mutations ◽

Mating Population ◽

Fixation Probabilities ◽

Genomic Regions ◽

Genomic Scans

Abstract It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites - both in the presence and absence of interference amongst deleterious mutations - and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.

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Genes Associated with SLE Are Targets of Recent Positive Selection

Autoimmune Diseases ◽

10.1155/2014/203435 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Paula S. Ramos ◽

Stephanie R. Shaftman ◽

Ralph C. Ward ◽

Carl D. Langefeld

Keyword(s):

Natural Selection ◽

Positive Selection ◽

Lupus Erythematosus ◽

Genetic Basis ◽

Ethnic Disparities ◽

Future Research ◽

Risk Alleles ◽

Recent Positive Selection ◽

Risk Variants ◽

Genomic Regions

The reasons for the ethnic disparities in the prevalence of systemic lupus erythematosus (SLE) and the relative high frequency of SLE risk alleles in the population are not fully understood. Population genetic factors such as natural selection alter allele frequencies over generations and may help explain the persistence of such common risk variants in the population and the differential risk of SLE. In order to better understand the genetic basis of SLE that might be due to natural selection, a total of 74 genomic regions with compelling evidence for association with SLE were tested for evidence of recent positive selection in the HapMap and HGDP populations, using population differentiation, allele frequency, and haplotype-based tests. Consistent signs of positive selection across different studies and statistical methods were observed at several SLE-associated loci, includingPTPN22,TNFSF4,TET3-DGUOK,TNIP1,UHRF1BP1,BLK, andITGAMgenes. This study is the first to evaluate and report that several SLE-associated regions show signs of positive natural selection. These results provide corroborating evidence in support of recent positive selection as one mechanism underlying the elevated population frequency of SLE risk loci and supports future research that integrates signals of natural selection to help identify functional SLE risk alleles.

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Genomic Targets of Positive Selection in Giant Mice from Gough Island

Molecular Biology and Evolution ◽

10.1093/molbev/msaa255 ◽

2020 ◽

Author(s):

Bret A Payseur ◽

Peicheng Jing

Keyword(s):

Positive Selection ◽

Reference Population ◽

Demographic Model ◽

Missense Mutations ◽

Applied Machine Learning ◽

Gough Island ◽

Regulatory Mutations ◽

Approximate Bayesian ◽

Genomic Regions ◽

Gene Ontologies

Abstract A key challenge in understanding how organisms adapt to their environments is to identify the mutations and genes that make it possible. By comparing patterns of sequence variation to neutral predictions across genomes, the targets of positive selection can be located. We applied this logic to house mice that invaded Gough Island, an unusual population that shows phenotypic and ecological hallmarks of selection. We used massively parallel short-read sequencing to survey the genomes of 14 Gough Island mice. We computed a set of summary statistics to capture diverse aspects of variation across these genome sequences, used approximate Bayesian computation to reconstruct a null demographic model, and then applied machine learning to estimate the posterior probability of positive selection in each region of the genome. Using a conservative threshold, 1,463 5kb windows show strong evidence for positive selection in Gough Island mice but not in a mainland reference population of German mice. Disproportionate shares of these selection windows contain genes that harbor derived nonsynonymous mutations with large frequency differences. Over-represented gene ontologies in selection windows emphasize neurological themes. Inspection of genomic regions harboring many selection windows with high posterior probabilities pointed to genes with known effects on exploratory behavior and body size as potential targets. Some genes in these regions contain candidate adaptive variants, including missense mutations and/or putative regulatory mutations. Our results provide a genomic portrait of adaptation to island conditions and position Gough Island mice as a powerful system for understanding the genetic component of natural selection.

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