Biomedical subjects

J I Weller

Publications and source records attributed to J I Weller.

At least 19 recordsLinked to original sources

PubMed2006

Estimation of the number of genetic markers required for individual animal identification accounting for genotyping errors.

Nearly all studies that consider the power of exclusion for individual identification using genetic markers ignore the possibility of erroneous genotypes, although individual genotype error rates are approximately 1% for microsatellites. Single nucleotide polymorphisms (SNPs) have lower error rates, but because of their lower information content, more SNPs than microsatellites will be required to obtain the same power of exclusion for traceability. In this study, we accounted for genotyping mistakes by requiring at least two discrepancies to reject a match. Exclusion probabilities were computed analytically and by simulation. A microsatellite with five alleles was approximately comparable in exclusion power to 2-2.25 SNPs. At least eight SNPs were required to achieve a 99% probability of rejection for a match between two individuals, while with 25 SNPs there was a <1% chance for a match between any of five million individuals.

Alleles↗

PubMed2006

Genetic analysis of persistency in the israeli holstein population by the multitrait animal model.

Persistency was defined as the predicted milk production 180 d after peak divided by peak production (in %). Heritability of persistency in a multitrait analysis including parities 1 through 5 increased from 0.16 to 0.27 from first through third parity, and then declined through fifth parity. Genetic correlations for persistency between consecutive parities were all > 0.8. First-parity genetic correlations of the traits included in the Israeli selection index with persistency were all < 0.1, except for fertility and herdlife, which were 0.20 and 0.25; whereas second-parity genetic correlations of persistency with the 3 milk production traits were all > 0.34, and the genetic correlation with fertility was only 0.10. The genetic correlation between second-parity persistency and herdlife was 0.58. Persistency in the Israeli Holstein population was analyzed by the multitrait animal model. The genetic trend since 1985 for the multiparity index was 0.22% persistency/yr, even though there was no direct selection on persistency.

Animals↗

PubMed2006

Short communication: a polymorphism in ABCG2 in Bos indicus and Bos taurus cattle breeds.

A single nucleotide change (A/C) in exon 14 is capable of encoding a substitution of tyrosine-581 to serine (Y581S) in the ABCG2 (ATP binding cassette, subfamily G, member 2) gene and affects milk production traits. The ABCG2(A) allele decreases milk yield and increases protein and fat concentration. The allele frequencies were determined in 32 Bos taurus and 3 Bos indicus breeds; ABCG2(A) was predominant in all populations. This allele approached fixation in 23 out of 35 breeds, including all 3 Bos indicus breeds. The ABCG2(C) allele was found in the Belgian Blue (beef), Belgian Blue Mix, British Friesian, Bohemian Red, East Anatolian Red, German Angus, German Black Pied, German Brown, German Simmental, Israeli Holstein, Menorquina, and US Holstein breeds. Thus, the genetic gain expected from selection for ABCG2(A) may be limited. The detection of ABCG2(C) only in Bos taurus breeds may indicate that ABCG2(A) is the ancestral allele, and that the Y581S substitution occurred after the separation of the Bos indicus and Bos taurus lineages.

ATP-Binding Cassette Transporters↗

PubMed2005

Detection of quantitative trait loci influencing conformation traits and calving ease in Holstein-Friesian cattle.

An extension of our previous genome scan of a North American Holstein-Friesian population was conducted to identify quantitative trait loci (QTL) affecting conformation traits. Resource families consisted of 1404 sons of 10 elite sires. Genome coverage was estimated to be 2713.5 cM (90%) for 406 markers using a granddaughter design. Regression interval mapping was used to detect QTL affecting 22 conformation traits, including body, udder, feet and legs, and dairy conformation as well as calving ease. Analysis of the families jointly identified 41 chromosome-wise significant QTL influencing conformation traits and 3 significant QTL influencing calving ease on 20 chromosomes. The false discovery rate method was used to account for multiple testing and 3/4 of the suggestive and 5/6 of significant QTL should be real effects. Fourteen of the 44 QTL were significant at the genome-wise level. Comparison of these results with other published reports identifies common QTL affecting conformation traits. Regions on 10 chromosomes appear to affect multiple traits, including conformation, milk production, and somatic cell score, within these particular US Holstein families. Additional work is needed to determine the precise locations of the QTL and select positional candidate genes influencing these traits.

Animals↗

PubMed2004

Bovine umbilical hernia maps to the centromeric end of Bos taurus autosome 8.

Twelve bull calves were produced by mating elite Israeli cows to "Glenhapton Enhancer", a Canadian Holstein bull. The frequency of umbilical hernia (UH) in the progeny of the sons ranged from 1 to 21%, consistent with the hypothesis that Enhancer is the carrier of major dominant or codominant gene with partial penetrance for UH. Five sons of Enhancer produced progeny with >10% frequency of UH including sire 3259, whereas progeny of three sons had <3% UH. A total of 116 grand-progeny of Enhancer, all progeny of 3259, were genotyped for 59 microsatellites spanning the 29 bovine autosomes. Of these offspring, 41 were affected. Significant differences in paternal allele frequencies between the affected and unaffected progeny groups were found for marker BMS1591 on bovine chromosome 8 (BTA8). The UH-associated paternal allele originated from Enhancer. The chromosomal segment associated with UH was more precisely mapped between UWCA47, on the centromeric end of BTA8 and RM321, 12 cM from the centromere. A maximum LOD score of 3.84 was obtained 2.5 cM from the centromere with a support interval of 8 cM. Haplotype analysis of eight sons of Enhancer suggested that the UH gene is located in the centromeric end of BTA8 beyond ARO71/ARO72. Thus, by integrating the results from progeny of sire 3259 and sons of Enhancer the location of the UH gene was further refined to the BTA8 segment between ARO71/ARO72 and UWCA47.

Animals↗

PubMed2004

Detection of quantitative trait loci affecting milk production, health, and reproductive traits in Holstein cattle.

We report putative quantitative trait loci affecting female fertility and milk production traits using the merged data from two research groups that conducted independent genome scans in Dairy Bull DNA Repository grandsire families to identify quantitative trait loci (QTL) affecting economically important traits. Six families used by both groups had been genotyped for 367 microsatellite markers covering 2713.5 cM of the cattle genome (90%), with an average spacing of 7.4 cM. Phenotypic traits included PTA for pregnancy rate and daughter deviations for milk, protein and fat yields, protein and fat percentages, somatic cell score, and productive life. Analysis of the merged dataset identified putative quantitative trait loci that were not detected in the separate studies, and the pregnancy rate PTA estimates that recently became available allowed detection of pregnancy rate QTL for the first time. Sixty-one putative significant marker effects were identified within families, and 13 were identified across families. Highly significant effects were found on chromosome 3 affecting fat percentage and protein yield, on chromosome 6 affecting protein and fat percentages, on chromosome 14 affecting fat percentage, on chromosome 18 affecting pregnancy rate, and on chromosome 20 affecting protein percentage. Within-family analysis detected putative QTL associated with pregnancy rate on six chromosomes, with the effect on chromosome 18 being the most significant statistically. These findings may help identify the most useful markers available for QTL detection and, eventually, for marker-assisted selection for improvement of these economically important traits.

Animals↗

PubMed2004

A complete genome scan of the Israeli Holstein population for quantitative trait loci by a daughter design.

Eleven Israeli Holstein families including 5221 cows were analyzed by a daughter design for eight economic traits: milk, fat and protein production, fat and protein percentage, somatic cell score (SCS), herd-life, and female fertility. The cows were genotyped for 73 microsatellites with maximum spacing between markers of 53 cM. There were 86,304 informative genotypes. Preliminary analysis was by ANOVA of each trait, with the marker effect nested within sire. Significance was determined by controlling the false discovery rate at 0.4, after excluding markers with genome-wide significance for at least a single trait, and traits without any significant effects at this level. Thus, four markers on chromosomes 6 and 14 and female fertility were excluded. There remained 40 significant marker-trait combinations, and it is expected that 24 of these are true effects. To perform interval mapping for the families with significant contrasts, 21 additional markers were genotyped on chromosomes 2, 7, and 27. The bootstrap confidence intervals for gene effect did not include zero for protein percent on chromosome 2 and fat yield, protein yield, and SCS on chromosome 7. Quantitative trait locus heterozygosity was 33%, which is consistent with the hypothesis that only two alleles are segregating with unequal allele frequency.

Animals↗

PubMed2004

Genetic analysis of the Israeli Holstein dairy cattle population for production and nonproduction traits with a multitrait animal model.

Milk, fat, and protein production, somatic cell score (SCS), and female fertility in the Israeli Holstein dairy cattle population were analyzed using a multitrait animal model (AM) with parities 1 through 5 as separate traits. Female fertility was measured as the inverse of the number of inseminations to conception in percent. Variance components were estimated using both the repeatability AM and multitrait AM. The multitrait heritabilities for individual parities were greater than the heritabilities from the repeatability AM, and heritabilities decreased with an increase in parity number. Heritabilities were higher for production traits, lower for SCS, and lowest for female fertility. The genetic correlations were higher than the environmental correlations. Genetic correlations between parities decreased with an increase in the difference in parity number, but all were greater than 0.5. The environmental correlations were higher for production traits, lower for SCS, and close to zero for female fertility. In the analysis of the complete milk recorded population, genetic trends from the repeatability and multitrait models were very similar. The genetic trend for SCS was economically unfavorable until 1993, and favorable since then. The genetic trend for female fertility was close to zero, but the annual environmental trend was -0.2%. The multitrait lactation model is an attractive compromise between repeatability lactation models, which do not account for maturing trends across parities, and test-day models, which are much more demanding computationally.

Animals↗

PubMed2004

Factors affecting incorrect paternity assignment in the Israeli Holstein population.

A total of 6040 Israeli Holstein cows from 181 Kibbutz herds listed as progeny of 11 sires were genotyped for 104 microsatellites. Seventeen markers were deleted due to a frequency of erroneous genotypes >1%, leaving 160,470 valid genotypes. Conflicts between the putative sire and daughter in at least 2 markers and for at least 10% of the markers genotyped per cow were required to reject paternity. Cows that did not meet the requirements for paternity confirmation or rejection were deleted from further analysis. The frequency of rejected paternity was 11.7%. The effects of recorded sire, birth year, geographical region, herd, and inseminator on the frequency of paternity rejection were analyzed with linear and nonlinear models. Only the effects of inseminator and recorded sire were significant in all models tested that included these effects. The main causes of incorrect paternity recording appear to be inseminator recording mistakes, and possibly mistakes with respect to semen labeling at the AI institutes. Incorrect paternity recording due to multiple inseminations by different sires could explain, at most, 20% of the paternity mistakes. Instituting a system of quality control, especially at the level of the inseminator, should reduce paternity errors to no more than 8%, and increase genetic progress by at least 1%.

Alleles↗

PubMed2003

Analysis of vaginal swabs for paternity testing and marker-assisted selection in cattle.

Blood is the standard source for DNA analysis, but requires venipuncture of cows by veterinarian and tedious and costly DNA extraction. A procedure was developed for sampling of vaginal cells from cows, establishing a cell lysis protocol using robotics, and applying fluorescent analysis of genetic markers. Two insemination technicians collected vaginal cells from 254 elite Israeli Holstein cows located in 152 herds using commercial Catch-All sample collection brushes. Cells were lysed in a 400-microliters solution, and 5 microliters was used as template for polymerase chain reaction (PCR). Sensitivity of the PCR was enhanced using only 1 microliter of lysed cells. Eight markers of the International Society of Animal Genetics paternity panel were amplified in four separate PCR. ILSTS039, a marker for a quantitative trait loci on BTA14, was amplified in a separate reaction. Genotypes from one to nine genetic markers were obtained for 253 out of 254 samples, and 244 cows had genotypes for at least three markers (96%). Cows that did not inherit either paternal allele for at least two loci were considered not to be daughters of the sire listed. Fifteen cows met this criterion, for a paternity misidentification rate of 6.25%. The frequency of allele 225 of ILSTS039, which was associated with increased milk fat content, was 11.1% in the bull-dam population, similar to the 12% found in the cow population in Israel. The use of vaginal cells for genetic analysis is accurate, as demonstrated by replicated analysis and by comparison to individual and population analysis based on DNA derived from blood.

Alleles↗

PubMed2003

Population-wide analysis of a QTL affecting milk-fat production in the Israeli Holstein population.

A population-wide linkage disequilibrium on bovine chromosome 14 between microsatellite ILSTS039 and DGAT1, a putative quantitative trait locus affecting milk production traits, was found in the Israeli Holstein population. A total of 394 bulls were genotyped for both DGAT1 and ILSTS039, and 1747 cows were genotyped for ILSTS039. The ILSTS039 allele termed "225," and the DGAT1 K allele (substitution of a lysine residue with alanine), were associated with decreased milk production, and increased fat production and fat and protein percent. The number of 225 ILSTS039 and K DGAT1 alleles per individual were the same for 80% of the bulls genotyped. From the effects associated with cows homozygous for the 225 allele, the effect of the quantitative trait locus appears to be approximately codominant. The substitution effect was 0.16% fat. Genotype probabilities for the quantitative gene were determined for the entire Israeli Holstein milk-recorded population, including 507,725 cows and 1442 bulls, using segregation analysis. Overall frequency of the allele that increased fat percent was 8.9% in cows and 15.5% in bulls. The frequency of this allele decreased from 1981 until 1990, from 15 to 5%, and since has increased to 10%. The effects estimated on the population-wide analyses of both cows and bulls were similar to the effect associated with DGAT1 in the daughters of genotyped bulls. Modified animal model evaluations were computed for the entire population with the effect of this gene included in the model. The correlations between the modified and standard animal model evaluations for all traits were > 0.99.

Acyltransferases↗

PubMed2001

Generation and exploration of a dense genetic map in a region of a QTL affecting corpora lutea in a Meishan x Yorkshire cross.

Previously genomic scans revealed quantitative trait loci (QTL) on porcine Chromosome 8 (SSC8) as significantly affecting the number of corpora lutea (CL) in swine. In one study, statistical evidence for the putative QTL was found in the chromosomal region defined by the microsatellites (MS) SW205, SW444, SW206, and SW29. A Yeast Artificial Chromosome library was screened by using the corresponding primers for clones containing these MS by PCR. From five positive YAC clones, 10 additional MS were isolated and mapped to SSC8 with the INRA-University of Minnesota porcine Radiation Hybrid (IMpRH) panel. The genetic map position of the QTL has been refined by addition of these 10 markers. The QTL evaluation included pedigrees of F2-intercross Meishan x Yorkshire design, with phenotypic data of 108 F2 female offspring and genotypic data for 29 MS markers on SSC8. The analysis was performed by using the least squares regression method. The calculated QTL effect for CL obtained by the multilocus least squares method showed a maximum test statistic (F value = 13.98) at position 99 cM between three MS derived from YACs containing SW205 and SW1843 spanning an interval of 7.1 cM. The point-wise (nominal) P-value was 5.21 x 10-6 corresponding to a genome-wide P-value of 0.009. The additive QTL effect explained 17.4% of the phenotypic variance.

Animals↗

PubMed2001

Multiple quantitative trait locus analysis of bovine chromosome 6 in the Israeli Holstein population by a daughter design.

Nine Israeli Holstein sire families with 2978 daughters were analyzed for quantitative trait loci effects on chromosome 6 for five milk production traits by a daughter design. All animals were genotyped for 2 markers. The three families with significant effects were genotyped for up to 10 additional markers spanning positions 0-122 cM of BTA6. Two sires were segregating for a locus affecting protein and fat percentage near position 55 cM with an estimated substitution effect of 0.18% protein, which is equivalent to one phenotypic standard deviation. This locus was localized to a confidence interval of 4 cM. One of these sires was also heterozygous for a locus affecting milk, fat, and protein production near the centromere. The hypothesis of two segregating loci was verified by multiple regression analysis. A third sire was heterozygous for a locus affecting milk and protein percentage near the telomeric end of the chromosome. Possible candidates for the major quantitative gene near position 55 cM were determined by comparative mapping. IBSP and SSP1 were used as anchors for the orthologous region on human chromosome 4. Twelve genes were detected within a 2-Mbp sequence. None of these genes have been previously associated with lactogenesis.

Animals↗

PubMed2000

Effect of misidentification on genetic gain and estimation of breeding value in dairy cattle populations.

The effect of pedigree errors on estimated breeding value and genetic gain for a sex-limited trait with heritability of 0.25 was evaluated. Ten populations of 100,000 milking cows were simulated with correct paternity identification for all animals, and 10 populations were simulated with 10% incorrect paternal identification. The initial populations consisted of 100,000 unrelated individuals, and simulations were continued for 20 yr. The BLUP genetic evaluations were computed every year by an animal model analysis for each complete population. Estimated breeding values for the populations with 10% incorrect paternity were biased, especially in the later generations. Genetic gains were 4.3% higher with correct paternity identification. Reduction of pedigree errors by paternity confirmation of daughters of test sires by DNA microsatellites may result in considerable economic benefits, depending on the cost of testing in each country.

Animals↗

PubMed1999

A genome scan for QTL influencing milk production and health traits in dairy cattle.

A genome scan was conducted in the North American Holstein-Friesian population for quantitative trait loci (QTL) affecting production and health traits using the granddaughter design. Resource families consisted of 1,068 sons of eight elite sires. Genome coverage was estimated to be 2,551 cM (85%) for 174 genotyped markers. Each marker was tested for effects on milk yield, fat yield, protein yield, fat percentage, protein percentage, somatic cell score, and productive herd life using analysis of variance. Joint analysis of all families identified marker effects on 11 chromosomes that exceeded the genomewide, suggestive, or nominal significance threshold for QTL effects. Large marker effects on fat percentage were found on chromosomes 3 and 14, and multimarker regression analysis was used to refine the position of these QTL. Half-sibling families from Israeli Holstein dairy herds were used in a daughter design to confirm the presence of the QTL for fat percentage on chromosome 14. The QTL identified in this study may be useful for marker-assisted selection and for selection of a refined set of candidate genes affecting these traits.

Animals↗

PubMed1999

An MspI polymorphism at the bovine growth hormone (bGH) gene is linked to a locus affecting milk protein percentage.

SSCP analysis of the bovine growth hormone (bGH) gene in Israel Holstein dairy cattle uncovered five intragenic haplotypes, denoted A to E. Of these, Haplotype E differed from the others at six fragments; one of which corresponded to the polymorphic MspI site in intron III, at which haplotype E carried the disabled MspI (-) allele. Haplotype E was observed in a single sire only, carrying haplotype A as the second bGH allele. In 523 daughters of this sire genotyped for the MspI polymorphism, heterozygous (+/-) as compared to homozygous (+/+) daughters, showed a significant increasing effect on protein percentage and kg protein per year; and a decreasing effect (P < 0.10) on milk somatic cell counts (MSSC). None of the daughters were homozygous (-/-), indicating that the frequency of this allele in the general population was essentially zero. Calculated skewness (g1) values for the two daughter groups differed significantly with (+/-) daughters showing negative skewness (in the direction of lower protein percentage), and (+/+) daughters positive skewness (in the direction of higher protein percentage). The direction of skewness in each group is indicative of the presence of a QTL having an increasing effect on milk protein percentage in coupling linkage with the MspI (-) allele in this sire, but at some distance from it. Maximum likelihood estimates of the proportion of recombination (r) between the putative QTL and bGH, and the allele substitution effect at the QTL (d), were r = 0.33, a = 0.07% protein, with standard errors 0.058 and 0.009% protein, respectively.

Animals↗

PubMed1999

Standardization and conversion of marker polymorphism measures.

Large scale gene mapping efforts in domestic animals have generated and mapped a large number of genetic markers that are useful for mapping quantitative trait and disease loci and for DNA diagnostic purposes such as parentage testing. Marker polymorphism is an important criterion for selecting genetic markers in planning experiment for mapping quantitative trait loci or for DNA diagnostic purposes. Current formulations of marker polymorphism measures are functions of marker allele frequencies. In this study, two measures of marker polymorphism that are available from gene mapping studies and do not require allele frequencies were proposed and analyzed: the observed polymorphic information content (PIC) and the observed family information content (FIC). The observed FIC was more stable than the observed PIC because the observed FIC is unaffected by the variation in the frequency of heterozygous parents. However, both FIC and PIC are dependent on the gene mapping design. The effective number of alleles is recommended as a tool to standardize marker polymorphism measures so that polymorphism of different markers can be compared on an equal basis, and to obtain a new polymorphism measure (such an exclusion probability) from an existing measure (such as FIC). The usage of the effective number of alleles to standardize FIC, PIC and exclusion probabilities is illustrated using genetic markers in a published linkage map.

Animals↗

PubMed1999

Genetic analysis of cow survival in the Israeli dairy cattle population.

The linear model method of VanRaden and Klaaskate for analyzing herd life was expanded. Information on conception and protein yield was included in the estimation of predicted herd life of Israeli Holsteins. Variance components were estimated by a multitrait animal model. Heritability was slightly higher for herd life than for number of parities, but genetic correlations were close to unity. Animal model heritability estimates of herd life were higher than were sire model estimates. The expected herd life of pregnant cows was 420 d greater than for open cows. Each kilogram of increase in protein yield increased expected herd life by 9.5 d. Heritability of expected herd life increased from 0.11 for cows 6 mo after first calving to 0.14 for cows 3 yr from first calving. The genetic correlation of expected and actual herd life increased from 0.87 for records cut after 6 mo to 0.99 for records cut 3 yr after first calving. Phenotypic correlations increased from 0.61 to 0.94. Sire genetic evaluations based on predicted herd life of live cows were strongly biased if all records were weighted equally, and evaluations derived by weighting incomplete records to account for the effects of current herd life on variance components were nearly unbiased.

Animals↗