Mapping of bovine ovulation rate QTL; an analytical approach for three generation pedigrees

Interval mapping was conducted for ovulation rate quantitative trait loci (QTL) using data from two related families from the United States Department of Agriculture, US Meat Animal Research Center twinning cattle herd. Both families are extended, three generation pedigrees from which records of sons, daughters and granddaughters were analysed. Both a method of analysis and results from that analysis are reported herein. Results from one of the two families (839802) were previously reported, but reanalysis here including the second, related family (839803) and a revised statistical model lessens support for the previously reported QTL. Results from interval mapping provided evidence for QTL in regions corresponding to those previously suggested for chromosomes 7 (chromosome-wise P < 0.05) and 19 (chromosome-wise P < 0.01) in the 839802 family, although statistical significance was reduced. In contrast to the previous report, evidence for a chromosome 5 QTL in the same family was greatly reduced while support for a QTL on chromosome 10 increased (chromosome-wise P < 0.01). Analysis of data from the related 839803 family failed to replicate evidence of QTL observed on either chromosome 7 or chromosome 19 in the 839802 family.     

Evidence for quantitative trait loci affecting twinning rate in North American Holstein cattle

Twinning in dairy cattle has been associated with many negative health and reproductive events that cause economic loss to the producer. Reports have suggested that twinning rates are increasing and that there may be a positive relationship between milk production and twinning frequency. Putative quantitative trait loci (QTL) for twinning and ovulation rate on bovine chromosomes 5, 7, 19 and 23 have been previously identified in other populations. The objective of this study was to detect and possibly confirm the existence and effects of these QTL in the North American Holstein population. Half-sib families of 20 North American Holstein sires with above average twinning rate predicted transmitting abilities (PTA) comprised the sample population under investigation. Twinning rate PTA values had been estimated from calving data. DNA extracted from semen samples was analysed using 45-61 microsatellite markers across the four chromosomes. Marker heterozygosity of the patriarchs averaged 62%. Evidence of twinning QTL was found in multiple families on chromosomes 5, 7 and 23 and in one family on chromosome 19. Four of the sires formed one three-generation family: one sire and three half-sib sons with sons of their own. This extended family was analysed with additional markers confirming a twinning QTL of significant size on chromosome 5.     

Mapping of a quantitative trait locus for beef marbling on bovine chromosome 9 in purebred Japanese black cattle

The goal of this study is to detect quantitative trait loci (QTL) for carcass traits applicable for a DNA-based breeding system in a Japanese Black cattle population. A purebred paternal half-sib family from a commercial line composed of 65 steers was initially analyzed using 188 informative microsatellites giving a 16-cM average interval covering 29 autosomes. A significant QTL for marbling was detected in the centromeric portion of bovine chromosome (BTA) 9. After additional marker genotyping across a larger sample size composed of 169 individuals, this locus was refined to a 20-cM confidence interval between microsatellites BM1227 (24 cM) and DIK2741 (50 cM) at a 1% chromosome-wise threshold. The allele substitution effect between Q and q for a beef marbling standard score (1 to 12 range) on BTA9 was 1.0 (5.7% of total phenotypic variance in QTL contribution in this family). This result provides a primary platform for a marker-assisted selection system of the beef marbling trait within the Japanese Black (Wagyu) cattle population.     

Genetic aspects of twinning in cattle

Twinning in cattle ranges from about 1% for beef breeds to about 4% for dairy breeds. The incidence of double births may have both positive and negative effects, which mainly depends on the purpose for which the cattle are raised. Because of freemartinism, as well as management problems connected e.g. with a greater risk of dystocia and retained placenta, it is an undesirable trait in dairy herds. In beef cattle, however, twinning can considerably increase the efficiency of production. Low heritability, a long generation interval for progeny testing, sex-limited expression and an unfavourable correlation with milk yield make twinning difficult to control by selection. Hence, it is the type of trait for which the identification of the genetic marker - quantitative trait loci (QTL) linkage and the implementation of marker-assisted selection in breeding strategies are expected to be especially beneficial. Searching for QTL influencing the reproductive rate in cattle was performed mainly in the US Meat Animal Research Center twinning herd and in the commercial Norwegian cattle population. Among several genome regions that appear to control twinning and ovulation rates, the most interesting seem to be chromosomes 5, 7, 19 and 23.     

Genome screen for twinning rate QTL in four North American Holstein families

The objective of this study was to identify twinning rate quantitative trait loci (QTL) by typing pooled samples in a preliminary screening followed by interval mapping to test QTL effects. Four elite North American Holstein half-sib sire families with high twinning rate predicted transmitting abilities (PTA) were used in this study. Chromosomes 5, 7, 19 and 23 were not genotyped as these chromosomes were scanned for QTL in these families in a previous study. DNA was extracted from phenotypically extreme sons in each sire family. Two pools were prepared from sons of sires in each phenotypic tail, two each for high and low PTA levels for twinning rates. Each pool contained DNA from 4 to 15% of all sons of the sire depending on family. A total of 268 fluorescently labelled microsatellite markers were tested for heterozygosity in sires. About 135--170 informative markers per family were genotyped using pooled DNA samples. Based on the preliminary evidence for potential twinning rate QTL from pooled typing, interval mapping was performed subsequently on 12 chromosomal regions by family combinations. Evidence of QTL for twinning rate was found in one family on BTA 21 and 29 at a chromosome-wide P<0.05 and on BTA 8, 10 and 14 with a chromosome-wide P<0.01.     

A search for quantitative trait loci for ovulation rate in cattle

Seventy-seven polymorphic microsatellites were analysed in offspring of three elite sires that were part of the foundation of an experimental population selected for twinning rate at the US Meat Animal Research Center, Clay Center, Nebraska. All females were assessed for ovulation rate by rectal palpation of corpora lutea over 8–10 consecutive oestrous cycles from approximately 12 to 18 months of age, and associations between ovulation rate and sire allele were examined in each of the three sire groups. A preliminary analysis was performed using selectively genotyped daughters of each sire. Markers found significant or approaching significance were also genotyped in all daughters, sons and granddaughters of these sires. A test of marker associations limited to the granddaughter data provided an independent confirmation of marker effect and significance relative to the initial test with daughter data. Putative ovulation rate quantitative trait loci were detected on chromosomes 7 and 23. Marker UWCA20 on chromosome 7 was associated with an effect in excess of one phenotypic standard deviation and accounted for approximately 10% of phenotypic variation ovulation rate. Marker CYP21 (steroid 21-hydroxylase) on chromosome 23 was associated with an effect of slightly less than half a phenotypic standard deviation and accounted for approximately 4% of phenotypic variation.     

Genome-wide scan for bovine twinning rate QTL using linkage disequilibrium

Twinning is a complex trait with negative impacts on health and reproduction, which cause economic loss in dairy production. Several twinning rate quantitative trait loci (QTL) have been detected in previous studies, but confidence intervals for QTL location are broad and many QTL are unreplicated. To identify genomic regions or genes associated with twinning rate, QTL analysis based on linkage combined with linkage disequilibrium (LLD) and individual marker associations was conducted across the genome using high-throughput single nucleotide polymorphism (SNP) genotypes. A total of 9919 SNP markers were genotyped with 200 sires and sons in 19 half-sib North American Holstein dairy cattle families. After SNPs were genotyped, informative markers were selected for genome-wide association tests and QTL searches. Evidence for twinning rate QTL was found throughout the genome. Thirteen markers significantly associated with twinning rate were detected on chromosomes 2, 5 and 14 ( P  < 2.3 × 10⁻⁵). Twenty-six regions on fourteen chromosomes were identified by LLD analysis at P  < 0.0007. Seven previously reported ovulation or twinning rate QTL were supported by results of single marker association or LLD analyses. Single marker association analysis and LLD mapping were complementary tools for the identification of putative QTL in this genome scan.     

Mapping of a Quantitative Trait Locus for Beef Marbling on Bovine Chromosome 9 in Purebred Japanese Black Cattle

The goal of this study is to detect quantitative trait loci (QTL) for carcass traits applicable for a DNA-based breeding system in a Japanese Black cattle population. A purebred paternal half-sib family from a commercial line composed of 65 steers was initially analyzed using 188 informative microsatellites giving a 16-cM average interval covering 29 autosomes. A significant QTL for marbling was detected in the centromeric portion of bovine chromosome (BTA) 9. After additional marker genotyping across a larger sample size composed of 169 individuals, this locus was refined to a 20-cM confidence interval between microsatellites BM1227 (24 cM) and DIK2741 (50 cM) at a 1% chromosome-wise threshold. The allele substitution effect between Q and q for a beef marbling standard score (1 to 12 range) on BTA9 was 1.0 (5.7% of total phenotypic variance in QTL contribution in this family). This result provides a primary platform for a marker-assisted selection system of the beef marbling trait within the Japanese Black (Wagyu) cattle population.     

Mapping quantitative trait loci for bovine ovulation rate

An elite, three-generation family from the USDA Meat Animal Research Center twinning population was examined for evidence of ovulation rate quantitative trait loci (QTL). This work was both a continuation of previously reported results suggesting evidence for ovulation rate QTL on bovine Chromosome (Chr) 7 and an extension of a genome-wide search for QTL. Additional markers were typed on Chr 7 to facilitate interval mapping and testing of the hypothesis of one versus two QTL on that chromosome. In addition, 14 other informative markers were added to a selective genotyping genome screening of this family, and markers exhibiting nominal significance were used to identify chromosomal regions that were then subjected to more exhaustive analysis. For Chr 7, a total of 12 markers were typed over a region spanning the proximal two-thirds of the chromosome. Results from interval mapping analyses indicated evidence suggestive of the presence of QTL (nominal P < 0.00077) within this region. Subsequent analysis with a model postulating two QTL provided evidence (P < 0.05) for two rather than one QTL on this chromosome. Preliminary analysis with additional markers indicated nominal significance (P < 0.05) for regions of Chrs 5, 10, and 19. Each of these regions was then typed with additional markers for the entire three-generation pedigree. Significant evidence (P < 0.000026) of ovulation rate QTL was found for Chrs 5 and 19, while support on Chr 10 failed to exceed a suggestive linkage threshold (P > 0.00077). Received: 14 May 1999 / Accepted: 14 October 1999     

Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping

A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.     

Quantitative Trait Loci Affecting Response to Crowding Stress in an F2 Generation of Rainbow Trout Produced Through Phenotypic Selection

Selective breeding programs for salmonids typically aim to improve traits associated with growth and disease resistance. It has been established that stressors common to production environments can adversely affect these and other traits which are important to producers and consumers. Previously, we employed phenotypic selection to create families that exhibit high or low plasma cortisol concentrations in response to crowding stress. Subsequent crosses of high × low phenotypes founded a multigenerational breeding scheme with the aim of dissecting the genetic basis for variation underlying stress response through the identification of quantitative trait loci (QTL). Multiple methods of QTL analyses differing in their assumptions of homozygosity of the causal alleles in the grandparental generation yielded similar results in the F₁ generation, and the analysis of two stress response phenotype measurement indexes were highly correlated. In the current study, we conducted a genome scan with microsatellites to detect QTL in the F₂ generation of two families created through phenotypic selection and having larger numbers of offspring than families screened in the previous generation. Seven suggestive and three significant QTL were detected, seven of which were not previously detected in the National Center for Cool and Cold Water Aquaculture germplasm, bringing the total number of chromosomes containing significant and suggestive stress response QTL to 4 and 15, respectively. One significant QTL which peaks at 7 cM on chromosome Omy12 spans 12 cM and explains 25 % of the phenotypic variance in family 2008052 particularly warrants further investigation. Five QTL with significant parent-of-origin effects were detected in family 2008052, including two QTL on Omy12. The 95 % confidence intervals for the remaining QTL we detected were broad, requiring validation and fine mapping with other genotyping approaches and mapping strategies. These results will facilitate identification of potential casual alleles that can be employed in strategies aimed at better understanding the genetic and physiological basis of stress responses to crowding in rainbow trout aquaculture production.     

Validation of SNP associations with bovine ovulation and twinning rate

Previous work identified SNP associations with twinning rate in the US Holstein population and developed a model for genomic prediction. The current study was conducted to assess the association of these SNPs with twinning rate and ovulation rate in a genetically diverse, outbred population selected for twinning and ovulation rate. A total of 18 SNPs that were components of a prediction equation for twinning rate in Holstein cattle were genotyped on 731 animals from the USDA Meat Animal Research Center production efficiency or twinning population. These 731 individuals were sires and dams well represented in the pedigrees of animals from the twinner population, and their genotypes were used in predicting genotypes for animals in the larger population (n = 16 035). Twinning rate and ovulation rate were analyzed in a two‐trait repeated records analysis with marker associations analyzed individually as fixed effects. Criteria for marker validation were effect estimate with a sign consistent with previous estimates and significance at a nominal P < 0.01. Of the 14 SNPs passing quality control assessments, only one was validated. A SNP in the 5′ flanking region of the IGF1 gene, discovered previously in a positional candidate gene analysis, was significantly associated with twinning rate in the USDA twinning population (P < 0.0002). This SNP may have utility in genomic prediction of twinning rate beyond the Holstein population.     

Development of microsatellite markers and comparative mapping for bovine chromosome 19

Previous research has mapped an ovulation rate quantitative trait locus (QTL) to bovine chromosome 19. In an effort to enhance comparative mapping information and develop additional markers for refined QTL mapping, microsatellite markers were developed in a targeted approach. A bovine bacterial artificial chromosome (BAC) library was screened for loci with either known or predicted locations on bovine chromosome 19. An average of 6.4 positive BAC were identified per screened locus. A total of 10 microsatellite markers were developed for five targeted loci with heterozygosity of 7-83% in a sample of reference family parents. The newly developed markers were typed on reference families along with four previously mapped marker loci and used to create a linkage map. Comparison of locus order between human and cattle provides support for previously observed rearrangement. One of the mapped loci myotubularin related protein 4 (MTMR4) potentially extends the proximal boundary of a conserved linkage group.     

Selection bias in quantitative trait loci mapping

A simulation study was performed to see whether selection affected quantitative trait loci (QTL) mapping. Populations under random selection, under selection among full-sib families, and under selection within a full-sib family were simulated each with heritability of 0.3, 0.5, and 0.7. They were analyzed with the marker spacing of 10 cM and 20 cM. The accuracy for QTL detection decreased for the populations under selection within full-sib family. Estimates of QTL effects and positions differed (P < .05) from their input values. The problems could be ignored when mapping a QTL for the populations under selection among full-sib families. A large heritability helped reduction of such problems. When the animals were selected within a full-sib family, the QTL was detected for the populations with heritability of 0.5 or larger using the marker spacing of 10 cM, and with heritability of 0.7 using the marker spacing of 20 cM. This study implied that when selection was introduced, the accuracy for QTL detection decreased and the estimates of QTL effects were biased. A caution was warranted on the decision of data (including selected animals to be genotyped) for QTL mapping.     

Quantitative trait loci affecting lactose and total solids on chromosome 6 in Brazilian Gir dairy cattle

Fourteen Brazilian Gir sire families with 657 daughters were analyzed for quantitative trait loci (QTL) on chromosome 6 affecting lactose and total solids. Cows and sires were genotyped with 27 microsatellites with a mean spacing between markers of 4.9 cM. We used a 1% chromosome-wide threshold for QTL qualification. A QTL for lactose yield was found close to marker MNB66 in three families. A QTL for total solid yield was identified close to marker BMS2508 in three families. A QTL for lactose percentage, close to marker DIK1182, was identified in two families. A QTL for total solid percentage, close to marker MNB208, was identified in four families. These QTLs could be used for selection of animals in dairy production systems.     

Genetic variation in the mannosidase 2B2 gene and its association with ovulation rate in pigs

Ovulation rate is an important phenotypic trait that is a critical component of litter size in pigs. Despite being moderately heritable in pigs, selection for increased ovulation rate is difficult because it is difficult to measure and is a sex-limited trait. A QTL for ovulation rate residing on the p-terminal end of pig chromosome 8 has been detected in a Meishan-cross resource population. Comparative analysis of this region yielded a positional candidate gene, mannosidase 2B2 (MAN2B2), for this QTL. The entire coding region of MAN2B2 was resequenced in the Meishan and White Composite founder animals of the resource population to identify SNPs. Eleven polymorphisms that alter the protein product of MAN2B2 were discovered and tested for statistical associations with ovulation rate in three generations of the resource population. The polymorphism located at position 1574 of the mRNA (D28521:c.1574A>G) was the most significant polymorphism tested (P = 0.00005) where the additive effect of the c.1574A allele was estimated to be -0.89 ova. This polymorphism was determined to be more significantly associated with ovulation rate than the breed-specific analysis conducted during the line-cross QTL discovery. The c.1574A>G marker was not associated with ovulation rate in an occidental population. Therefore, either MAN2B2 has a unique epistatic interaction within the Meishan-cross population or the c.1574A>G SNP is in linkage disequilibrium with the actual causative genetic variation in the Meishan-cross population.     

Genetic control of multiple births in low ovulating mammalian species

In mammals, litter size is a highly variable trait. Some species such as humans or cattle are monotocous, with one or sometimes two newborns per birth, whereas others, the polytocous species such as mice or pigs, are highly prolific and often produce a dozen newborns at each farrowing. In monotocous species, however, two or three newborns per birth may sometime be unwanted. In more polytocous species such as sheep or pigs, litter size is studied in order to increase livestock prolificacy. By contrast, twinning rates in humans or cattle may increase birth difficulties and health problems in the newborns. In this context, the aim of our review was to provide a clearer understanding of the genetic and physiological factors that control multiple births in low-ovulating mammalian species, with particular focus on three species: sheep, cattle, and humans, where knowledge of the ovulation rate in one may enlighten findings in the others. This article therefore reviews the phenotypic and genetic variability observed with respect to ovulation and twinning rates. It then presents the QTL and major genes that have been identified in each species. Finally, we draw a picture of the diversity of the physiological mechanisms underlying multiple ovulation. Although several major genes have been discovered in sheep, QTL detection methods in humans or cattle have suggested that the determinism of litter size is complex and probably involves several genes in order to explain variations in the number of ovulations.

     

Genetic control of multiple births in low ovulating mammalian species

In mammals, litter size is a highly variable trait. Some species such as humans or cattle are monotocous, with one or sometimes two newborns per birth, whereas others, the polytocous species such as mice or pigs, are highly prolific and often produce a dozen newborns at each farrowing. In monotocous species, however, two or three newborns per birth may sometime be unwanted. In more polytocous species such as sheep or pigs, litter size is studied in order to increase livestock prolificacy. By contrast, twinning rates in humans or cattle may increase birth difficulties and health problems in the newborns. In this context, the aim of our review was to provide a clearer understanding of the genetic and physiological factors that control multiple births in low-ovulating mammalian species, with particular focus on three species: sheep, cattle, and humans, where knowledge of the ovulation rate in one may enlighten findings in the others. This article therefore reviews the phenotypic and genetic variability observed with respect to ovulation and twinning rates. It then presents the QTL and major genes that have been identified in each species. Finally, we draw a picture of the diversity of the physiological mechanisms underlying multiple ovulation. Although several major genes have been discovered in sheep, QTL detection methods in humans or cattle have suggested that the determinism of litter size is complex and probably involves several genes in order to explain variations in the number of ovulations.     

RAPD和SSR两种标记构建的中国对虾遗传连锁图谱

利用RAPD和SSR分子标记结合拟测交策略,对中国对虾(Fenneropenaeuschinensis)“黄海1号”雌虾与野生雄虾作为亲本进行单对杂交产生的F1代,采用RAPD和SSR两种分子标记技术初步构建了中国对虾雌、雄遗传连锁图谱。对460个RAPD引物和44对SSR引物进行筛选,共选出61个RAPD引物和20对SSR引物,用于对父母本和82个F1个体进行遗传分析。共得到母本分离标记146个(RAPD标记128个,微卫星标记18个)和父本分离标记127个(RAPD标记109个,微卫星标记18个)。雌性图谱包括8个连锁群、9个三联体和14个连锁对,标记间平均间隔为11·28cM,图谱共覆盖1173cM,覆盖率为59·36%;雄性图谱包括10个连锁群、12个三联体和7个连锁对,标记间平均间隔为12·05cM,图谱共覆盖1144·6cM,覆盖率为62·01%。中国对虾遗传图谱的构建为其分子标记辅助育种、比较基因组作图及数量性状位点的定位与克隆奠定了基础。     

Fine mapping and single nucleotide polymorphism effects estimation on pig chromosomes 1, 4, 7, 8, 17 and X

Fine mapping of quantitative trait loci (QTL) from previous linkage studies was performed on pig chromosomes 1, 4, 7, 8, 17, and X which were known to harbor QTL. Traits were divided into: growth performance, carcass, internal organs, cut yields, and meat quality. Fifty families were used of a F2 population produced by crossing local Brazilian Piau boars with commercial sows. The linkage map consisted of 237 SNP and 37 microsatellite markers covering 866 centimorgans. QTL were identified by regression interval mapping using GridQTL. Individual marker effects were estimated by Bayesian LASSO regression using R. In total, 32 QTL affecting the evaluated traits were detected along the chromosomes studied. Seven of the QTL were known from previous studies using our F2 population, and 25 novel QTL resulted from the increased marker coverage. Six of the seven QTL that were significant at the 5% genome-wide level had SNPs within their confidence interval whose effects were among the 5% largest effects. The combined use of microsatellites along with SNP markers increased the saturation of the genome map and led to smaller confidence intervals of the QTL. The results showed that the tested models yield similar improvements in QTL mapping accuracy.