A new look at preventive care guidelines.
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Adult↗
Biomedical subjects
M Soller
Publications and source records attributed to M Soller.
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↗
DNA sequence of SSCP haplotypes at the bovine growth hormone (bGH) gene.
Previous studies using SSCP and PCR-RFLP methodologies uncovered nine polymorphic sites within the bGH gene, defining eight intragenic haplotypes falling into two main groups. In the present study we report the DNA sequence of these eight haplotypes. A total of 1494 bp were sequenced uncovering a total of 12 sequence variants. Haplotypes within groups differed among themselves at one or two sites, compared across groups, haplotypes of the two groups differed consistently at six sites, each of which was monomorphic within the respective groups. This comes to 4 differentiating sites per kb, suggesting that the two haplotype groups began to diverge about 400,000 years ago. This corresponds approximately to the estimated time of divergence of the Bos taurus and Bos indicus lineages, raising the possibility, supported by other evidence, that the two haplotype classes represent taurine and indicine haplotypes, respectively. Nucleotide sequence divergence of taurine and indicine genomes of this magnitude has far reaching implications with respect to QTL mapping and marker assisted selection in breeds derived from taurine x indicine crosses.
Animals↗
Differential and inefficient splicing of a broadly expressed Drosophila erect wing transcript results in tissue-specific enrichment of the vital EWG protein isoform.
In this report, we document an unusual mode of tissue-enriched gene expression that is primarily mediated by alternative and inefficient splicing. We have analyzed posttranscriptional regulation of the Drosophila erect wing gene, which provides a vital neuronal function and is essential for the formation of certain muscles. Its predominant protein product, the 116-kDa EWG protein, a putative transcriptional regulator, can provide all known erect wing-associated functions. Moreover, consistent with its function, the 116-kDa protein is highly enriched in neurons and is also observed transiently in migrating myoblasts. In contrast to the protein distribution, we observed that erect wing transcripts are present in comparable levels in neuron-enriched heads and neuron-poor bodies of adult Drosophila. Our analyses shows that erect wing transcript consists of 10 exons and is alternatively spliced and that a subset of introns are inefficiently spliced. We also show that the 116-kDa EWG protein-encoding splice isoform is head enriched. In contrast, bodies have lower levels of transcripts that can encode the 116-kDa protein and greater amounts of unprocessed erect wing RNA. Thus, the enrichment of the 116-kDa protein in heads is ensured by tissue-specific alternative and inefficient splicing and not by transcriptional regulation. Furthermore, this regulation is biologically important, as an increased level of the 116-kDa protein outside the nervous system is lethal.
Alternative Splicing↗
A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice.
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Amino Acid Sequence↗
Quantitative trait locus mapping in dairy cattle by means of selective milk DNA pooling using dinucleotide microsatellite markers: analysis of milk protein percentage.
"Selective DNA pooling" accomplishes quantitative trait locus (QTL) mapping through densitometric estimates of marker allele frequencies in pooled DNA samples of phenotypically extreme individuals. With poly(TG) microsatellites, such estimates are confounded by "shadow" ("stutter") bands. A correction procedure was developed on the basis of an observed linear regression between shadow band intensity and allele TG repeat number. Using this procedure, a selective DNA pooling study with respect to milk protein percentage was implemented in Israel-Holstein dairy cattle. Pools were prepared from milk samples of high and low daughters of each of seven sires and genotyped with respect to 11 markers. Highly significant associations with milk protein percentage were found for 5 of the markers; 4 of these markers confirmed previous reports. Selective DNA pooling accessed 80.6 and 48.3%, respectively, of the information that would have been available through individual selective genotyping or total population genotyping. In effect, the statistical power of 45,600 individual genotypings was obtained from 328 pool genotypings. This methodology can make genome-wide mapping of QTL accessible to moderately sized breeding organizations.
Animals↗
Comb size and estrogen levels toward the onset of lay in broiler and layer strain females under ad libitum and restricted feeding.
The time course of comb development and estrogen levels were compared in broiler (BX) and layer (LX) females that consumed feed ad libitum (A) or were subjected to quantitative feed restriction (R). The chicks were reared under short photoperiod [(6 h light (L):18 h dark (D)] until 22 wk of age. At this time, photoperiod was increased in one step to 8L:16 D, and then gradually increased until 14L:10D at 34 wk. There was a significant interaction between genetic type and feeding treatment, such that entry into lay of the LX-R and BX-R females was delayed by 1 and 4 wk, respectively, relative to the LX-A and BX-A birds. Mean comb size of LX-A birds began to increase while still under 6L:18D photoperiod; that of the other treatment groups did not begin to increase until photoperiod was shifted to 8L:16D. Comb size of individual LX-A, LX-R, and BX-A birds began to increase about 8 wk prior to individual onset of lay; that of BX-R birds about 11 wk prior to onset of lay. In all groups, estrogen levels remained low until 3 to 4 wk prior to onset of lay, when they showed a sharp increase. Following onset of lay, estrogen levels of all groups remained high. Critical day length of LX-A birds appears to be lower than that of BX-A birds. In addition, feed restriction per se appears to decrease photoperiod responsiveness of BX birds.
Aging↗
Genomic approaches to the improvement of disease resistance in farm animals.
As a result of the difficulties in improving disease resistance in farm animals by traditional phenotype selection, the achievement of such improvement is one of the most important applications of genome research. The major hurdle to this important goal is the collection of informative disease records to enable the segregation of disease resistance loci (DRL) to be traced in pedigrees. This paper reviews the principles for DRL identification by association analyses or by linkage analyses. Once linkage has been established, the location of the DRL may be further refined, a process which may eventually lead to the molecular characterisation of the causative gene(s) and mutation(s). A reliable map assignment of a DRL is sufficient for the practical utilisation of this knowledge, since the inheritance of the DRL can be traced by flanking markers. Marker-assisted selection concerns the use of linked markers for selection within populations, while marker-assisted introgression is used if DRL alleles are introgressed from a donor (resource) population.
Animals↗
Mating and sex peptide stimulate the accumulation of yolk in oocytes of Drosophila melanogaster.
Mating elicits two reactions in many insect females: egg deposition is increased and receptivity to males is reduced. Central to the control of receptivity and oviposition in Drosophila melanogaster is the sex peptide (SP), a 36-amino-acid peptide sex pheromone synthesized in the male accessory glands and transferred to the female during copulation. To identify regulatory mechanisms involved in the maintenance of the oviposition response, we have compared the effects of mating and SP application with respect to oogenesis. The distribution of the various stages of oogenesis in the ovary, yolk protein (YP) synthesis by the fat body, as well as YP content, uptake and synthesis by the ovary were investigated. Transcripts of the yolk protein genes (yp) were quantified by Northern blotting. Based on our results, we conclude that mating and SP injection into virgin females stimulate yp gene transcription in the fat body only moderately above the background level. However, uptake into the ovary and transcription of the yp genes in the ovary is strongly enhanced after either mating or SP injection. These data are supported by the finding that the abundance of the vitellogenic stage 10 oocytes is also increased. In contrast, early vitellogenic stages 8 and 9 of oogenesis are present in the same numbers in virgin, mated, and SP-injected females, which suggests a control point at about stage 9 determining vitellogenic oocyte progression. The finding that SP can elicit equally all changes observed after copulation suggests that in the sexually mature female it is the major component controlling and stimulating oogenesis after mating.
Animals↗
Simple sequence repeats as a source of quantitative genetic variation.
Most traits in biological populations appear to be under stabilizing selection, which acts to eliminate quantitative genetic variation. Yet, virtually all measured traits in biological populations continue to show significant quantitative genetic variation. The paradox can be resolved by postulating the existence of an abundant, though unspecified, source of mutations that has quantitative effects on phenotype, but does not reduce fitness. Does such a source actually exist? We propose that it does, in the form of repeat-number variation in SSRs (simple sequence repeats, of which the triplet repeats of human neurodegenerative diseases are a special case). Viewing SSRs as a major source of quantitative mutation has broad implications for understanding molecular processes of evolutionary adaptation, including the evolutionary control of the mutation process itself.
Animals↗
A simple method to calculate resolving power and confidence interval of QTL map location.
"Resolving power" is defined as the 95% confidence interval for quantitative trait locus (QTL) map location that would be obtained when scoring an infinite number of markers in a given constellation of a marker-QTL mapping experiment. Resolving power can serve as a close estimate of the confidence interval of QTL map location, as well as a guide to the lower efficient limit of marker spacing in an initial marker-QTL mapping experiment. In the present study, an extensive series of simulations was carried out to provide estimates of resolving power, for backcross (BC) and F2 designs, over a wide range of experimental sizes and of gene effects and dominance at the QTL. From the simulation results, the remarkably simple expressions, 3000/(mNd2) (where m = 1 for BC and m = 2 for F2; N = population size, and d = allele substitution effect) and 530/Nv (in terms of v, the proportion of variance explained), were obtained for estimating resolving power. These expressions can provide a convenient guide to planning marker spacing in BC and F2 marker-QTL linkage experiments and for placing confidence intervals about QTL map location obtained in such experiments.
Animals↗
Localization of genes controlling resistance to trypanosomiasis in mice.
Tsetse fly-transmitted trypanosomes (Trypanosoma spp.) cause "sleeping sickness' in man and have a serious impact on livestock-based agriculture in large areas of Africa. Multigene control of variation in susceptibility to trypanosomiasis is known to occur in mice, where the C57BI/6 (B6) strain is relatively resistant and the A/J (A) and Balb/c (B) strains are susceptible. Such resistance is also well described among several types of west African cattle. We report here the results of genome-wide scans for genes controlling this trait in the B6 mouse using crosses with two different susceptible strains. Regions on mouse chromosomes 5 and 17 were found to be important in determining resistance in both crosses while an additional region on chromosome 1 showed evidence of involvement in only one cross. We confirmed the size of the effect due to chromosome 17 in F3 intercross populations fixed for alternative parental chromosomes. The three loci are of large effect and account for most of the genetic variation in both F2 populations. We propose that they be designated Tir1, Tir2 and Tir3.
Animals↗
Inheritance and mapping of Compact (Cmpt), a new mutation causing hypermuscularity in mice.
During selection for protein content in mice at the Technical University of Berlin, individuals showing high protein content and a compact exterior were noted. Animals showing this "Compact" phenotype were separated to form a new line. The present investigations were carried out on a Hungarian subpopulation of this line, selected for maximum expression of the Compact phenotype, and apparently at fixation for the relevant genes. Fertility and viability of the Compact subpopulation was normal. As compared to normal mice, carcass percentage values for male and female Compact mice were 9.4 and 6.8% greater, respectively; and the muscle:bone weight ratio in males was 1.61-fold greater. The Compact phenotype showed variable expressivity and was of intermediate dominance in males, but almost fully recessive in females. The hypothesis that a single gene is solely responsible for the Compact phenotype was rejected by maximum likelihood analysis. Linkage mapping using selective DNA pooling located a single locus (denoted Cmpt) strongly associated with the Compact phenotype on mouse chromosome 1. Fine mapping, using individual selective genotyping and haplotype analysis, located Cmpt to the region between D1Mit375 and D1Mit21, approximately one third of the way to D1Mit21.
Animals↗
A PCR-based test for the presence of endogenous virus gene evA in chickens.
An endogenous virus, denoted evA, is present at high frequency in all brown egg layer lines. Using inverse polymerase chain reaction (PCR) based on the viral LTR regions, products were obtained containing cellular sequences 5' and 3' to the viral insertion point. PCR of chicken genomic DNA was carried out, using primers chosen from the 5' and 3' cellular sequences and a primer chosen from either the U3 or U5 portions of the viral LTR. Amplification of DNA from birds that did not carry evA with the primer triplets always gave a single 364 bp reaction product, interpreted as representing the flank-to-flank amplification product. Amplification of DNA from known homozygous or heterozygous evA carriers, with the same primer triplets, always gave both the expected junction product and 364 bp product. Therefore, these primer sequences can be used to distinguish evA carriers from non-carriers but cannot distinguish between homozygous and heterozygous evA carriers.
Alpharetrovirus↗
Minisatellite and microsatellite length variation at a complex bovine VNTR locus.
Length variation at the BTGL1 variable number of tandem repeat (VNTR) locus, which includes both minisatellite and microsatellite motifs, was examined in a wide sample of cattle. A total of 22 alleles were uncovered. The distribution of allele size variation implicated mechanisms involving both minisatellite and microsatellite sequences. This was confirmed by direct sequences of two alleles. Differences between the two alleles involved repeat number variation of microsatellite motifs and a complex event involving the minisatellite motif, but point mutations were not observed.
Animals↗
Genetic control of resistance to trypanosomiasis.
To map the genetic sources of trypanotolerance in mice, a linkage analysis of survival following trypanosome challenge was performed by selective genotyping in a large F2 population produced by crossing the resistant C57BL/6 and susceptible BALB/c inbred mouse lines. We report evidence of a chromosomal region of large effect, possibly comprising more than one resistance locus, on Chromosome 17; and of further loci on Chromosomes 1 and 5. Together, these genes can account for all of the difference between the mean parental phenotypes.
Animals↗
Association between SSCP haplotypes at the bovine growth hormone gene and milk protein percentage.
The bovine Growth Hormone gene (bGH) is an attractive candidate gene for milk production in cattle. Single-strand conformation polymorphisms at bGH were identified and used to define haplotype configurations at this gene in the Israeli Holstein dairy cattle population (Bos taurus) and in the parent animals of the International Bovine Reference Family Panel (a collection of B. taurus and B. indicus crosses). B. taurus and B. indicus haplotypes at the bGH gene differed qualitatively, confirming the previously proposed long evolutionary separation of these cattle subraces. Only a small number of bGH haplotypes were present in the Israel Holstein population. One of the haplotypes, apparently of B. indicus origin, was found to have a highly significant positive effect on milk protein percentage. This illustrates the utility of the haplotype approach for uncovering candidate gene involvement in quantitative genetic variation in agricultural populations. The strong effect of an indicine haplotype in a taurine background raises the possibility that indicine alleles at other candidate genes may comprise a genetic resource for improvement of taurine populations. It is proposed that haplotype analysis may be a useful adjunct to measures of genetic distance for evaluating rare breeds with respect to gene conservation.
Animals↗
Single-parent segregant pools for allocation of markers to a specified chromosomal region in outcrossing species.
Bulked co-segregant analysis is a method of rapidly allocating unmapped genetic markers to a specific chromosomal region. Although originally developed for utilization in populations derived from crosses between fully inbred lines, it has been proposed that co-segregant pools could also serve the same purpose in outbreeding populations, if individuals from only a single large family are pooled. Large, fully mapped, single-sire backcross and half-sib families are presently available as part of the international chicken and bovine reference family panels respectively. In this study, power and tests of significance for single-parent co-segregant analysis are derived for full-sib, single-parent back-cross and single-parent half-sib families, as a function of proportion of recombination between index marker and linked marker, pro-portion of single-parent alleles among the mates, number of individuals in each segregant pool and technical error variance. Power was found to be greater than 0.80 for many reasonable parameter combinations. The method is illustrated using microsatellite markers and a large single-sire bovine family, part of the international bovine reference family panel.
Alleles↗