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Biomedical subjects

J Hillel

Publications and source records attributed to J Hillel.

At least 19 recordsLinked to original sources

A consensus linkage map of the chicken genome.

A consensus linkage map has been developed in the chicken that combines all of the genotyping data from the three available chicken mapping populations. Genotyping data were contributed by the laboratories that have been using the East Lansing and Compton reference populations and from the Animal Breeding and Genetics Group of the Wageningen University using the Wageningen/Euribrid population. The resulting linkage map of the chicken genome contains 1889 loci. A framework map is presented that contains 480 loci ordered on 50 linkage groups. Framework loci are defined as loci whose order relative to one another is supported by odds greater then 3. The possible positions of the remaining 1409 loci are indicated relative to these framework loci. The total map spans 3800 cM, which is considerably larger than previous estimates for the chicken genome. Furthermore, although the physical size of the chicken genome is threefold smaller then that of mammals, its genetic map is comparable in size to that of most mammals. The map contains 350 markers within expressed sequences, 235 of which represent identified genes or sequences that have significant sequence identity to known genes. This improves the contribution of the chicken linkage map to comparative gene mapping considerably and clearly shows the conservation of large syntenic regions between the human and chicken genomes. The compact physical size of the chicken genome, combined with the large size of its genetic map and the observed degree of conserved synteny, makes the chicken a valuable model organism in the genomics as well as the postgenomics era. The linkage maps, the two-point lod scores, and additional information about the loci are available at web sites in Wageningen (http://www.zod.wau.nl/vf/ research/chicken/frame_chicken.html) and East Lansing (http://poultry.mph.msu.edu/).

Animals↗

Genetic mapping of quantitative trait loci affecting susceptibility to Marek's disease virus induced tumors in F2 intercross chickens.

Marek's disease (MD) is a lymphoproliferative disease caused by the MD virus (MDV), which costs the poultry industry nearly $1 billion annually. To identify quantitative trait loci (QTL) affecting MD susceptibility, the inbred lines 6(3) (MD resistant) and 7(2) (MD susceptible) were mated to create more than 300 F2 chickens. The F2 chickens were challenged with MDV JM strain, moderately virulent) at 1 wk of age and assessed for MD susceptibility. The QTL analysis was divided into three stages. In stage 1, 65 DNA markers selected from the chicken genetic maps were typed on the 40 most MD-susceptible and the 40 most MD-resistant F2 chickens, and 21 markers residing near suggestive QTL were revealed by analysis of variance (ANOVA). In stage 2, the suggestive markers plus available flanking markers were typed on 272 F2 chickens, and three suggestive QTL were identified by ANOVA. In stage 3, using the interval mapping program Map Manager and permutation tests, two significant and two suggestive MD QTL were identified on four chromosomal subregions. Three to five loci collected explained between 11 and 23% of the phenotypic MD variation, or 32-68% of the genetic variance. This study constitutes the first report in the domestic chicken on the mapping of non-major histocompatibility complex QTL affecting MD susceptibility.

Analysis of Variance↗

Map-based quantitative trait locus identification.

Poultry gene mappers chose microsatellites as the main source of genetic markers for poultry genome mapping, similar to the marker type used for other farm animals, laboratory animals, and humans. Optimal strategies for applying DNA markers in poultry populations are discussed, including the number of markers to be used, genome representation, population structure, choice of markers, population size, statistical stringency for association between markers and quantitative trait loci (QTL), and biological verification of a linkage. It is shown that an efficient strategy should be based on a combination of a low stringent statistical test for the existence of linkage between a marker and QTL and an appropriate genetic test for the discrimination between true and false linkage. The source of the genetic variation to be used is discussed and, as an illustration, three types of resource populations are presented. The informativeness of different matings using various genotypes of the parents are considered and it appears that selection of markers based on the heterozygosity of the sire is the most efficient marker screening approach.

Animals↗

Heterosis and DNA fingerprinting in chickens.

Enhancement of performance in traits of economic importance by use of heterosis (hybrid vigor) is routine in poultry breeding. There is, however, no reliable method to predict the level of heterosis that will occur from the mating of individuals from two populations. DNA fingerprints (DFP) were used as a measure of genetic distance between mating pairs of chickens where each individual of a pair was from a different population; the association between that genetic distance and levels of heterosis in the offspring of those pairs was assessed for juvenile BW and for age at production of first egg. There was an inverse relationship between DFP bandsharing level of parents and heterosis in their offspring, suggesting that DFP may be useful in predicting heterosis.

Aging↗

Development of a genetic map of the chicken with markers of high utility.

Microsatellites are tandem duplications with a simple motif of one to six bases as the repeat unit. Microsatellites provide an excellent opportunity for developing genetic markers of high utility because the number of repeats is highly polymorphic, and the assay to score microsatellite polymorphisms is quick and reliable because the procedure is based on the polymerase chain reaction (PCR). We have identified 404 microsatellite-containing clones of which 219 were suitable as microsatellite markers. Primers for 151 of these microsatellites were developed and used to detect polymorphisms in DNA samples extracted from the parents of two reference populations and three resource populations. Sixty, 39, 46, 49, and 61% of the microsatellites exhibited length polymorphisms in the East Lansing reference population, the Compton reference population, resource population No. 1 (developed to identify resistance genes to Marek's disease), resource population No. 2 (developed to identify genes involved in abdominal fat), and resource population No. 3 (developed to identify genes involved in production traits), respectively. The 91 microsatellites that were polymorphic in the East Lansing reference population were genotyped and 86 genetic markers were eventually mapped. In addition, 11 new random amplified polymorphic DNA (RAPD) markers and 24 new markers based on the chicken CR1 element were mapped. The addition of these markers increases the total number of markers on the East Lansing genetic map to 273, of which 243 markers are resolved into 32 linkage groups. The map coverage within linkage groups is 1,402 cM with an average spacing of 6.7 cM between loci. The utility of the genetic map is greatly enhanced by adding 86 microsatellite markers. Based on our current map, approximately 2,550 cM of the chicken genome is within 20 cM of at least one microsatellite marker.

Animals↗

Genetic diversity among commercial chicken populations estimated from DNA fingerprints.

Blood samples were obtained from parental pure lines representing a large majority of commercial meat-type (broiler) and white egg layer lines presently available in the USA. From blood mixes of each line, DNA was extracted and a DNA fingerprint pattern characteristic of that line was produced. Additionally, DNA fingerprints representing wild jungle fowl and two randombred control populations were produced. Three analyses were conducted: 1) among broiler sire lines, jungle fowl, and one control line; 2) among broiler dam lines, jungle fowl, and one control line; and 3) among parental lines of white egg layers, jungle fowl, and the second control line. Bandsharing levels were calculated, providing an estimate of genetic diversity among lines. Conclusions were that, at present, broiler sire lines, broiler dam lines, and parental lines of white egg layers that make up the majority of commercial breeding populations available in the USA contain a considerable reservoir of genetic diversity.

Animals↗

DNA fingerprint bands applied to linkage analysis with quantitative trait loci in chickens.

An efficient approach to detect association between quantitative traits and bands of DNA fingerprint patterns uses intra-family tail analysis, which compares fingerprints of DNA mixes from individuals at the two tails of a phenotypic distribution. In analysis of 67 paternal half-sibs of a meat-type chicken family, of 57 sire bands generated by two probes, one sire-specific band (S6.6) was associated with abdominal fat deposition. The band effect was estimated by a linear model analysis to be 0.88 standard deviations, or about 30% of the family mean. The association between band S6.6 and abdominal fat was further examined by testing progeny of paternal half-sibs of the chickens which were used in the tail analysis, establishing genetic linkage between the DNA marker and a genetic locus affecting abdominal fat deposition.

Adipose Tissue↗

Evaluating linkage between DNA fingerprint bands and quantitative traits in chickens: interactions.

This study assessed the influence of background genome on expression of genes linked to DNA fingerprint (DFP) bands in chickens. Two experimental lines of White Plymouth Rocks previously selected for high or low 8-wk body weight were crossed to produce two F1 males that served as heads of two sire families. Each of these sires was mated to three hens from an unrelated White Leghorn population to produce progeny in which quantitative traits of 4-, 8-, and 12-wk body weight and shank length at 12 wk were measured. The DFP patterns were produced for all individuals in the study. For the 12 sire-specific DFP bands (common to both F1 sires but not found in the dams), each offspring was classified as having or not having each band. Then, an analysis of variance was conducted for each DFP sire band with sex, hatch, dam family, and presence or absence of the sire band as main effects. Interactions between dam family and presence or absence of sire band were also tested. Of 48 possible analyses of variance (12 sire bands by 4 quantitative traits), 3 resulted in significant effects due to sire band, and 2 indicated significant interactions. Thus, associations of a DFP band and a gene coding for a quantitative trait were present, but, in some cases, the expression of the trait differed, depending on the dam family in which it occurred. These data suggest that associations between DFP bands and quantitative traits may not be consistent in different genetic backgrounds.

Animals↗

Restriction fragment length polymorphism analysis of major histocompatibility complex class IV (B-G) genotypes in meat-type chickens.

Restriction fragment length polymorphism (RFLP) was used as a molecular genotyping approach to characterize differences in major histocompatibility complex class IV genes in meat-type chickens. A high level of polymorphism was observed following digestion with each of the two restriction endonucleases PvuII and BglII. Examination of DNA from 54 chickens revealed 23 polymorphic fragments. Application of RFLP techniques in the analysis of family groups should make possible the determination of B-G genotypes in the meat type chickens.

Animals↗

Deoxyribonucleic acid fingerprint bands linked to loci coding for quantitative traits in chickens.

Efficacy of DNA fingerprint (DFP) bands in marker-assisted selection programs for quantitative traits in chickens was evaluated. A cross between two populations of White Plymouth Rock chickens that had been selected for 31 generations for high (HW) or low (LW) 8-wk body weight served as the base population for the experiment. Full- and half-sib families were produced over four generations and 400 offspring were measured for body weight at 8 wk (BW8) and shank length at 12 wk of age (SL12). Distributions were constructed for each quantitative trait in offspring of one F1 sire. The DFP produced from mixed blood of the individuals within each tail of the distribution were compared. From a total of 13 DFP bands that were disparate in intensity between the tails, four bands were chosen for analysis. Matings were made between males and females based on the presence or absence of these bands, but were limited to individuals that were within .5 standard deviation of the mean for the distribution of a particular trait. Quantitative traits of the resulting progeny were analyzed to determine whether parental type (presence or absence of the DFP band) influenced expression of the trait in the offspring. One band out of the four tested was associated with SL12, was an effective predictor of phenotype for both SL12 and BW8, and appeared to be inherited in a dominant fashion.

Animal Husbandry↗

Genetic factors accountable for line-specific DNA fingerprint bands in quail.

DNA fingerprints, prepared from mixes of DNA of individuals sampled from lines of Japanese quail selected for high or low 4-week body weight, were used to evaluate the relative contribution of several evolutionary forces to genetic diversity among populations. Comparisons between lines--two replicates of each selection direction and a control unselected line--were used to determine the frequency of line-specific DNA fingerprint bands produced by each of three major evolutionary forces: 1) mutation; 2) genetic drift; 3) selection. The latter force is expected to generate line-specific bands only if there is linkage disequilibrium between DNA fingerprint loci and quantitative loci (QTLs) controlling body weight. Using probes 33.6 and R18.1, an average of 48.4 DNA fingerprint bands in each line were analyzed. On average, 27.8 bands were found to be line-specific among the 96.8 (2 x 48.4) bands analyzed in an average comparison between pairs of lines. Based on the frequencies of line-specific bands in each particular comparison, it was calculated that 21% of the line-specific bands were due to mutation, 11% due to a single genetic drift event, 11% due to selection, 21% due to the combined effects of genetic drift and selection, 22% due to double independent events of genetic drift, and 14% due to undefined factors. Although evidence was found for a high frequency of genetic changes attributable to genetic drift, and a higher than expected frequency of linkage disequilibrium, the emphasis of this report is on the methodology suggested rather than on the particular results.

Animals↗

DNA fingerprints of farm animals generated by microsatellite and minisatellite DNA probes.

A multi-locus DNA probe, R18.1, derived from a bovine genomic library, detected DNA fingerprints of highly polymorphic loci in hybridization to genomic DNA from poultry and sheep, and of moderate polymorphic loci in cattle and human DNA. The average numbers of detected bands in chickens and sheep were 27.8 and 21.4, and the average band sharing levels were 0.25 and 0.33, respectively. In hybridization to cattle and human DNA, the results were less polymorphic; nevertheless, individual identification is feasible using probe R18.1. The results obtained by R18.1 were compared to results obtained by Jeffreys minisatellite probe 33.6 and two microsatellite oligonucleotides, (GT)12 and (GTG)5. The total number of detected loci using probes R18.1 and 33.6 were estimated in chickens through family analysis of broilers and the maximal number of detectable loci was calculated.

Alleles↗

Deoxyribonucleic acid fingerprint comparisons between selected populations of chickens.

A pair of lines of White Plymouth Rock chickens selected for high or low juvenile body weight, a pair of White Leghorn chickens selected for high or low antibody response to sheep erythrocytes, and an F1 cross between each pair of lines, were used to produce DNA fingerprints (DFP). These DFP were prepared by mixing equal amounts of DNA from several individuals of a particular population, resulting in a DFP characteristic of the population. The populations provided individuals of known genetic relationships and inbreeding levels to evaluate the sensitivity of the DFP technique with DNA mixing. Levels of band sharing between breeds were lowest, those between selected lines within a breed were intermediate, and those between the selected lines and their F1 crosses were highest. These results show that DFP analysis is sensitive to several levels of genetic relationship.

Animals↗

DNA fingerprints applied to gene introgression in breeding programs.

An application of DNA fingerprints (DFP) for gene introgression in breeding programs of both farm animals and plants is proposed. DFP loci, detectable by minisatellite probes, are extremely polymorphic. Individuals have unique patterns of DFP and thus can be selected for maximal genomic similarity to the recipient line, and minimal similarity to the donor line, using their DFP patterns as the criterion for similarity. This genomic selection (GS) can be performed at generations BC1, BC2 or both, and thus significantly reduce the required number of backcross generations in introgression breeding programs. The association between genomic and DFP similarity is demonstrated. Theoretical distributions and variances of the relative percentages of the donor and recipient genomes as the basis for the GS approach are presented.

Alleles↗

DNA fingerprints of chickens selected for high and low body weight for 31 generations.

Two lines of White Plymouth Rock chickens that have been divergently selected for 8-week body weight for 31 generations were compared for patterns of DNA fingerprints (DFP). Digestion of DNA with HinfI and hybridization to Jeffreys' minisatellite probe 33.6 resulted in DFPs that were relatively similar within lines (bandsharing = 0.50) and less similar between lines (bandsharing = 0.22). Analyses of scorable DFP bands produced by mixing DNA from individuals within lines indicated that 48% were line-specific. Causes for the differences in DFP patterns between lines and for occurrence of line-specific bands for the two lines divergently selected for body weight are discussed.

Animals↗

DNA fingerprints of poultry.

Human minisatellite probes cross-hybridize to DNA of several species of poultry (chicken, duck, turkey and goose), and detect high levels of polymorphism. The resulting DNA fingerprints are individual specific, and allow the discrimination even between closely related birds. The pattern of poultry DNA fingerprints is different from that of humans and other animals, having a higher average proportion of large DNA fragments. Pedigree analysis revealed a low number of allelic pairs of variable DNA fragments, indicating that most of the alleles are unresolved in the DNA fingerprint or too small to be detected. The total number of detectable loci in broilers, using probe 33.6, was estimated as 62, of which 13 loci are on average scoreable and available for use. Poultry DNA fingerprints can be used for individual identification, linkage studies and as an aid in breeding programmes.

Alleles↗

[Pharmacologic interventions in agitated mentally retarded patients].

Aggressive behavior of mental retardates is a frequent problem which semiological description is very polymorphic. Some psychiatric etiologies are listed, and then the different aspects of idiopathic aggressive behavior are described. These aspects give guidelines for more specific treatments which are further reviewed. Preferential indications and side effects are described for each in a way to suggest a therapeutic strategy. At the end, legal aspects involved are briefly exposed.

Humans↗