Runs of homozygosity and inbreeding in thyroid cancer.
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ABSTRACT:
SUBMITTER: Thomsen H
PROVIDER: S-EPMC4794977 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
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Project description:Pedigree information was traditionally used to assess inbreeding. The availability of high-density marker panels provides an alternative to assess inbreeding, particularly in the presence of incomplete and error-prone pedigrees. Assessment of autozygosity across chromosomal segments using runs of homozygosity (ROH) has emerged as a valuable tool to estimate inbreeding due to its general flexibility and ability to quantify the chromosomal contribution to genome-wide inbreeding. Unfortunately, the identification of ROH segments is sensitive to the parameters used during the search process. These parameters are heuristically set, leading to significant variation in the results. The minimum length required to identify an ROH segment has major effects on the estimation of inbreeding and inbreeding depression, yet it is arbitrarily set. To overcome this limitation, a search algorithm to approximate mutation enrichment was developed to determine the minimum length of ROH segments. It consists of finding genome segments with significant effect differences in trait means between animals with high and low burdens of autozygous intervals with a specific length. The minimum length could be determined heuristically as the smallest interval at which a significant signal is detected. The proposed method was tested in an inbred Hereford cattle population genotyped for 30,220 SNPs. Phenotypes recorded for six traits were used for the approximation of mutation loads. The estimated minimum length was around 1 Mb for yearling weight (YW) and average daily gain (ADG) and 4 Mb for birth weight and weaning weight. These trait-specific thresholds estimated using the proposed method could be attributed to a trait-dependent effect of homozygosity. The detection of significant inbreeding effects was well aligned with the estimated thresholds, especially for YW and ADG. Although highly deleterious alleles are expected to be more frequent in recent inbreeding (long ROH), short ROH segments (<5 Mb) could contain a large number of less deleterious mutations with substantial joint effects on some traits (YW and ADG). Our results highlight the importance of accurate estimation of the ROH-based inbreeding and the necessity to consider a trait-specific minimum length threshold for the identification of ROH segments in inbreeding depression analyses. These thresholds could be determined using the proposed method provided the availability of phenotypic information.
| S-EPMC7846130 | biostudies-literature
Project description:Cashmere goats are valuable genetic resources which are famous worldwide for their high-quality fiber. Runs of homozygosity (ROHs) have been identified as an efficient tool to assess inbreeding level and identify related genes under selection. However, there is limited research on ROHs in cashmere goats. Therefore, we investigated the ROH pattern, assessed genomic inbreeding levels and examined the candidate genes associated with the cashmere trait using whole-genome resequencing data from 123 goats. Herein, the Inner Mongolia cashmere goat presented the lowest inbreeding coefficient of 0.0263. In total, we identified 57,224 ROHs. Seventy-four ROH islands containing 50 genes were detected. Certain identified genes were related to meat, fiber and milk production (FGF1, PTPRM, RERE, GRID2, RARA); fertility (BIRC6, ECE2, CDH23, PAK1); disease or cold resistance and adaptability (PDCD1LG2, SVIL, PRDM16, RFX4, SH3BP2); and body size and growth (TMEM63C, SYN3, SDC1, STRBP, SMG6). 135 consensus ROHs were identified, and we found candidate genes (FGF5, DVL3, NRAS, KIT) were associated with fiber length or color. These findings enhance our comprehension of inbreeding levels in cashmere goats and the genetic foundations of traits influenced by selective breeding. This research contributes significantly to the future breeding, reservation and use of cashmere goats and other goat breeds.
| S-EPMC11047310 | biostudies-literature
Project description:Inbreeding is often an inevitable outcome of strong directional artificial selection but on average it reduces population fitness with increased frequency of recessive deleterious alleles. Runs of homozygosity (ROH) representing genomic autozygosity that occur from mating between selected and genomically related individuals may be able to reveal the regions affecting fitness. To examine the influence of genomic autozygosity on fitness, we used a genome-wide association test to evaluate potential negative correlations between ROH and daughter pregnancy rate (DPR) or somatic cell score (SCS) in US Jersey cattle. In addition, relationships between changes of local ROH and inbreeding coefficients (F) were assessed to locate genomic regions with increased inbreeding. Despite finding some decreases in fertility associated with incremental increases in F, most emerging local ROH were not significantly associated with DPR or SCS. Furthermore, the analyses of ROH could be approximated with the most frequent haplotype(s), including the associations of ROH and F or traits. The analysis of the most frequent haplotype revealed that associations of ROH and fertility could be accounted for by the additive genetic effect on the trait. Thus, we suggest that a change of autozygosity is more likely to demonstrate footprints of selected haplotypes for production rather than highlight the possible increased local autozygosity of a recessive detrimental allele resulting from the mating between closely related animals in Jersey cattle.
| S-EPMC4496098 | biostudies-literature
Project description:Runs of homozygosity (ROH) are continuous homozygous segments from the common ancestor of parents. Evaluating ROH pattern can help to understand inbreeding level and genetic basis of important traits. In this study, three representative cattle populations including Leiqiong cattle (LQC), Lufeng cattle (LFC) and Hainan cattle (HNC) were genotyped using the Illumina BovineHD SNPs array (770K) to assess ROH pattern at genome wide level. Totally, we identified 26,537 ROH with an average of 153 ROH per individual. The sizes of ROH ranged from 0.5 to 53.26Mb, and the average length was 1.03Mb. The average of FROH ranged from 0.10 (LQC) to 0.15 (HNC). Moreover, we identified 34 ROH islands (with frequency > 0.5) across genome. Based on these regions, we observed several breed-specific candidate genes related to adaptive traits. Several common genes related to immunity (TMEM173, MZB1 and SIL1), and heat stress (DNAJC18) were identified in all three populations. Three genes related to immunity (UGP2), development (PURA) and reproduction (VPS54) were detected in both HNC and LQC. Notably, we identified several breed-specific genes related to sperm development (BRDT and SPAG6) and heat stress (TAF7) in HNC, and immunity (CDC23 and NME5) and development (WNT87) in LFC. Our findings provided valuable insights into understanding the genomic homozygosity pattern and promoting the conservation of genetic resources of Chinese indigenous cattle.
| S-EPMC9409551 | biostudies-literature
Project description:The Caqueteño Creole (CAQ) is a native breed of cattle from the Caquetá department (Colombia), adapted to tropical conditions, which is extremely important to production systems in those regions. However, CAQ is poorly studied. In this sense, population structure studies associated with runs of homozygosity (ROH) analysis would allow for a better understanding of CAQ. Through ROH analysis, it is possible to reveal genetic relationships between individuals, measure genome inbreeding levels, and identify regions associated with traits of economic interest. Samples from a CAQ population (n = 127) were genotyped with the Bovine HD BeadChip (777,000 SNPs) and analyzed with the PLINK 1.9 program to estimate FROH and ROH islands. We highlighted a decrease in inbreeding frequency for FROH 4−8 Mb, 8−16 Mb, and >16 Mb classes, indicating inbreeding control in recent matings. We also found genomic hotspot regions on chromosomes 3, 5, 6, 8, 16, 20, and 22, where chromosome 20 harbored four hotspots. Genes in those regions were associated with fertility and immunity traits, muscle development, and environmental resistance, which may be present in the CAQ breed due to natural selection. This indicates potential for production systems in tropical regions. However, further studies are necessary to elucidate the CAQ production objective.
| S-EPMC9318017 | biostudies-literature
Project description:Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.) The association of individual SNPs indicated no differences in the proportions of homozygous individuals among short-time survivors (STSs) and long-time survivors (LTSs). (II.) The analysis revealed differences among the populations for the number of ROHs per person and the total and average length of ROHs per person and among LTSs and STSs for the number of ROHs per person. (III.) Common ROHs at particular genomic positions were nominally more frequent among LTSs than in STSs. Common ROHs showed significant evidence for natural selection (iHS, Tajima's D, Fay-Wu's H). Most regions could be linked to genes related to BC progression or treatment. (IV.) Results were supported by a higher level of inbreeding among LTSs. Our results showed that an increased level of homozygosity may result in a preference of individuals during BC treatment. Although common ROHs were short, variants within ROHs might favor survival of BC and may function in a recessive manner.
| S-EPMC4642301 | biostudies-literature
Project description:BACKGROUND:Runs of homozygosity (ROH) are continuous homozygous segments of the DNA sequence. They have been applied to quantify individual autozygosity and used as a potential inbreeding measure in livestock species. The aim of the present study was (i) to investigate genome-wide autozygosity to identify and characterize ROH patterns in Gyr dairy cattle genome; (ii) identify ROH islands for gene content and enrichment in segments shared by more than 50% of the samples, and (iii) compare estimates of molecular inbreeding calculated from ROH (FROH), genomic relationship matrix approach (FGRM) and based on the observed versus expected number of homozygous genotypes (FHOM), and from pedigree-based coefficient (FPED). RESULTS:ROH were identified in all animals, with an average number of 55.12 ± 10.37 segments and a mean length of 3.17 Mb. Short segments (ROH1-2 Mb) were abundant through the genomes, which accounted for 60% of all segments identified, even though the proportion of the genome covered by them was relatively small. The findings obtained in this study suggest that on average 7.01% (175.28 Mb) of the genome of this population is autozygous. Overlapping ROH were evident across the genomes and 14 regions were identified with ROH frequencies exceeding 50% of the whole population. Genes associated with lactation (TRAPPC9), milk yield and composition (IRS2 and ANG), and heat adaptation (HSF1, HSPB1, and HSPE1), were identified. Inbreeding coefficients were estimated through the application of FROH, FGRM, FHOM, and FPED approaches. FPED estimates ranged from 0.00 to 0.327 and FROH from 0.001 to 0.201. Low to moderate correlations were observed between FPED-FROH and FGRM-FROH, with values ranging from -0.11 to 0.51. Low to high correlations were observed between FROH-FHOM and moderate between FPED-FHOM and FGRM-FHOM. Correlations between FROH from different lengths and FPED gradually increased with ROH length. CONCLUSIONS:Genes inside ROH islands suggest a strong selection for dairy traits and enrichment for Gyr cattle environmental adaptation. Furthermore, low FPED-FROH correlations for small segments indicate that FPED estimates are not the most suitable method to capture ancient inbreeding. The existence of a moderate correlation between larger ROH indicates that FROH can be used as an alternative to inbreeding estimates in the absence of pedigree records.
| S-EPMC5759835 | biostudies-literature
Project description:The primary purpose of the current study was to assess the genetic diversity, runs of homozygosity (ROH) and ROH islands in a Chinese composite pig and explore hotspot regions for traces of selection. First, we estimated the length, number, and frequency of ROH in 262 Xidu black pigs using the Porcine SNP50 BeadChip and compared the estimates of inbreeding coefficients, which were calculated based on ROHs (FROH) and homozygosity (FHOM). Our result shows that a total of 7,248 ROH exceeding 1Mb were detected in 262 pigs. In addition, Sus scrofa chromosome (SSC) 8 and SSC10, respectively, has the highest and lowest chromosome coverage by ROH. These results suggest that inbreeding estimation based on total ROH may be a useful method, especially for crossbreed or composite populations. We also calculated an inbreeding coefficient of 0.077 from the total ROH. Eight ROH islands were found in this study. These ROH islands harbored genes associated with fat deposition, muscular development, reproduction, ear shape, and adaptation, such as TRAF7, IGFBP7, XPO1, SLC26A8, PPARD, and OR1F1. These findings may help to understand the effects of environmental and artificial selection on the genome structure of composite pigs. Our results provide a basis for subsequent genomic selection (GS), and provides a reference for the hybrid utilization of other pig breeds.
| S-EPMC8440853 | biostudies-literature
Project description:Runs of homozygosity (ROH) are defined as long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROH and their length are indicators of the level and origin of inbreeding. In this study, we analysed SNP chip datasets (obtained using the Axiom OrcunSNP Array) of a total of 702 rabbits from 12 fancy breeds and four meat breeds to identify ROH with different approaches and calculate several genomic inbreeding parameters. The highest average number of ROH per animal was detected in Belgian Hare (~150) and the lowest in Italian Silver (~106). The average length of ROH ranged from 4.001 ± 0.556 Mb in Italian White to 6.268 ± 1.355 Mb in Ermine. The same two breeds had the lowest (427.9 ± 86.4 Mb, Italian White) and the highest (921.3 ± 179.8 Mb, Ermine) average values of the sum of all ROH segments. More fancy breeds had a higher level of genomic inbreeding (as defined by ROH) than meat breeds. Several ROH islands contain genes involved in body size, body length, pigmentation processes, carcass traits, growth, and reproduction traits (e.g.: AOX1, GPX5, IFRD1, ITGB8, NELL1, NR3C1, OCA2, TRIB1, TRIB2). Genomic inbreeding parameters can be useful to overcome the lack of information in the management of rabbit genetic resources. ROH provided information to understand, to some extent, the genetic history of rabbit breeds and to identify signatures of selection in the rabbit genome.
| S-EPMC9826494 | biostudies-literature
Project description:BackgroundConsecutive 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 ~?65,000 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.ResultsIn 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).ConclusionThe 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.
| S-EPMC7011551 | biostudies-literature