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Biomedical subjects

M Ron

Publications and source records attributed to M Ron.

At least 19 recordsLinked to original sources

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↗

Evaluation of eight commercial tests for Mycoplasma pneumoniae antibodies in the absence of acute infection.

Eight commercially available tests for Mycoplasma pneumoniae (Serodia-Myco II, Labsystems IgM and IgG EIA, IgM and IgG LISA tests, ImmunoWell IgG test and SeroMP IgM and IgG) were compared using 204 single sera from healthy individuals. IgM peaked in late childhood and then declined, while IgG rose progressively into adulthood. Inter-assay agreement was poor. Positivity in Serodia-Myco II and LISA IgG was associated with blood group or Coombs positivity, suggesting non-specific reactions. The study confirmed that single serum serology is unsuitable for the diagnosis of M. pneumoniae infection, and that commercially available tests need further improvement.

Adolescent↗

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↗

The neuropsychology of variant CJD: a comparative study with inherited and sporadic forms of prion disease.

OBJECTIVE: To assess cognitive function in variant Creutzfeldt-Jakob disease (vCJD). We describe the neuropsychological profiles of 10 cases and compare these data with cross sectional data obtained from patients with histologically confirmed sporadic CJD and cases with inherited prion disease with confirmed mutations in the prion protein gene. METHODS: Patients referred to the Specialist Cognitive Disorders Clinic at the National Hospital for Neurology and Neurosurgery and the National Prion Clinic at St Mary's Hospital, London for further investigation of suspected CJD were recruited into the study. The neuropsychological test battery evaluated general intelligence, visual and verbal memory, nominal skills, literacy skills, visual perception and visuospatial functions, and visuospatial and executive function. RESULTS: The results indicate that moderate to severe cognitive decline is a characteristic feature of vCJD. Specifically, verbal and visual memory impairments and executive dysfunction were pervasive in all disease groups. Nominal skills were impaired in variant and sporadic CJD, significantly so when compared with the inherited prion disease group. Perceptual impairment was less frequent in the vCJD group than in the sporadic and inherited groups. CONCLUSION: This study confirms the occurrence of generalised cognitive decline in patients with vCJD. Although decline in cognitive function ultimately affects all domains, there is a suggestion that some components of visual perception may be spared in vCJD. The results also suggest that nominal function may be preserved in some cases with inherited prion disease.

Adult↗

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↗

Genome-scan analysis for quantitative trait loci in an F2 tilapia hybrid.

We searched for genetic linkage between DNA markers and quantitative trait loci (QTLs) for innate immunity, response to stress, biochemical parameters of blood, and fish size in an F2 population derived from an interspecific tilapia hybrid (Oreochromis mossambicusx O. aureus). A family of 114 fish was scanned for 40 polymorphic microsatellite DNA markers and two polymorphic genes, covering approximately 80% of the tilapia genome. These fish had previously been phenotyped for seven immune-response traits and six blood parameters. Critical values for significance were P <0.05 with the false discovery rate (FDR) controlled at 40%. The genome-scan analysis resulted in 35 significant marker-trait associations, involving 26 markers in 16 linkage groups. In a second experiment, nine markers were re-sampled in a second family of 79 fish of the same species hybrid. Seven markers (GM180, GM553, MHC-I, UNH848, UNH868, UNH898 and UNH925) in five linkage groups (LG 1, 3, 4, 22 and 23) were associated with stress response traits. An additional six markers (GM47, GM552, UNH208, UNH881, UNH952, UNH998) in five linkage groups (LG 4, 16, 19, 20 and 23) were verified for their associations with immune response traits, by linkage to several different traits. The portion of variance explained by each QTL was 11% on average, with a maximum of 29%. The average additive effect of QTLs was 0.2 standard deviation units of stress response traits and fish size, with a maximum of 0.33. In three linkage groups (LG 1, 3 and 23) markers were associated with stress response, body weight and sex determination, confirming the location of QTLs reported by several other studies.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗