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Biomedical subjects

T Schaap

Publications and source records attributed to T Schaap.

At least 19 recordsLinked to original sources
PubMed2005

Evidence for a major gene affecting the transition from normoglycaemia to hyperglycaemia in Psammomys obesus.

We investigated the mode of inheritance of nutritionally induced diabetes in the desert gerbil Psammomys obesus (sand rat), following transfer from low-energy (LE) to high-energy (HE) diet which induces hyperglycaemia. Psammomys selected for high or low blood glucose level were used as two parental lines. A first backcross generation (BC(1)) was formed by crossing F(1) males with females of the diabetes-prone line. The resulting 232 BC(1) progeny were assessed for blood glucose. All progeny were weaned at 3 weeks of age (week 0), and their weekly assessment of blood glucose levels proceeded until week 9 after weaning, with all progeny maintained on HE diet. At weeks 1 to 9 post weaning, a clear bimodal distribution statistically different from unimodal distribution of blood glucose was observed, normoglycaemic and hyperglycaemic at a 1:1 ratio. This ratio is expected at the first backcross generation for traits controlled by a single dominant gene. From week 0 (prior to the transfer to HE diet) till week 8, the hyperglycaemic individuals were significantly heavier (4--17%) than the normoglycaemic ones. The bimodal blood glucose distribution in BC(1) generation, with about equal frequencies in each mode, strongly suggests that a single major gene affects the transition from normo- to hyperglycaemia. The wide range of blood glucose values among the hyperglycaemic individuals (180 to 500 mg/dl) indicates that several genes and environmental factors influence the extent of hyperglycaemia. The diabetes-resistant allele appears to be dominant; the estimate for dominance ratio is 0.97.

Animals↗
PubMed2001

Distinctive genetic signatures in the Libyan Jews.

Unlinked autosomal microsatellites in six Jewish and two non-Jewish populations were genotyped, and the relationships among these populations were explored. Based on considerations of clustering, pairwise population differentiation, and genetic distance, we found that the Libyan Jewish group retains genetic signatures distinguishable from those of the other populations, in agreement with some historical records on the relative isolation of this community. Our methods also identified evidence of some similarity between Ethiopian and Yemenite Jews, reflecting possible migration in the Red Sea region. We suggest that high-resolution statistical methods that use individual multilocus genotypes may make it practical to distinguish related populations of extremely recent common ancestry.

Arabs↗
PubMed1997

Intensive plasmapheresis for severe thrombotic thrombocytopenic purpura: long-term clinical outcome.

Plasma exchange is of proven efficacy in the treatment of thrombotic thrombocytopenic purpura (TTP). In most series, less than 40 plasma exchanges (PE) were required for treatment and as many as two thirds of patients had permanent residual organ damage. We report on 4 patients who required very intensive PE for the resolution of TTP (37, 68, 102 and 108 procedures, respectively). The maximum number of PE procedures per attack was 102. None of these patients has any permanent sequellae of TTP (other than those associated with splenectomy, which was performed on all patients). Two of the female patients had uncomplicated pregnancies since resolution of the disease. We conclude that even highly refractory cases of TTP can have an excellent clinical outcome with intense PE therapy.

Adult↗
PubMed1995

Confidentiality in counseling for X-linked conditions.

Genetic counseling in a synthetic fragile-X family is used to illustrate some dilemmas which may arise from the genetic counselor's wish to respect the patient's confidence. What is the counselor's obligation towards family members who are unaware that they are carriers? Should the counselor try to avoid disclosing information concerning such family members to the patient, and if so-how? May the future father of an affected fetus be prevented from participating in the reproductive decisions concerning that fetus, out of respect for the mother's wishes?

Chromosomes, Human, X↗
PubMed1991

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↗
PubMed1991

Hunter syndrome in Jews in Israel: further evidence for prenatal selection favoring the Hunter allele.

Among all the Jewish families with Hunter patients in Israel, 10 were Ashkenazi or Moroccan in origin. In those families, there was a paucity of new mutations. In addition, a significant deviation of the segregation ratio between the Hunter gene and the normal allele was demonstrated among the offspring of heterozygous mothers or siblings of affected children in these families. These results confirm and extend our previous observations suggesting selection in favor of the X chromosome carrying the Hunter allele among Ashkenazi and Moroccan Jews.

Alleles↗
PubMed1990

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↗
PubMed1989

The role of recombination in the evolvement of the fragile X mutation.

The frequency of recombination in the regions adjacent to the fragile X locus was studied in two groups of carriers: daughters of transmitting males and transmitters of maternally inherited fragile X chromosomes. Approximately one-half of the offspring of the former and one quarter of the offspring of the latter are recombinant. Recombinants and parentals are equally distributed among affected and normal offspring in the two groups. These results indicate that crossing-over at or around the fragile X locus occurs in every meiosis in daughters of transmitting males, although the recombinant chromatids do not necessarily carry the fragile X mutation. Hence, crossing-over is unequivocally associated with, but is not the direct cause of, the transition from the primary genetic lesion to the final mutation.

Crossing Over, Genetic↗
PubMed1988

Cytological evidence of defective template in the fragile X chromosome.

In cells of fragile X patients, the changed X segment may appear as a poorly staining region or a gap, or as a deletion, involving one or both chromatids. To find out whether the fragile site represents an incompletely replicated DNA sequence, as has been suggested recently, we analyzed the four chromatids of methotrexate-induced endoreduplicated fragile X chromosomes. Our main observations were: (1) a deleted chromatid was never internal to a poorly staining one; (2) an endoreduplicated X chromosome with a fragile site never included a normal chromatid. These results can be explained by assuming that DNA at the fragile site, when replicated in the presence of methotrexate, may undergo defective replication and give rise to improperly packaged chromatin, appearing as a chromatid with a poorly staining region or a gap in the following metaphase. The same DNA may fail to function as a template in the following S-phase and give rise to a chromatid with a single-stranded segment, appearing as a deleted chromatid in the following metaphase.

Cell Cycle↗
PubMed1987

Proximal and distal regulatory elements that influence in vivo expression of a cell cycle-dependent human H4 histone gene.

We have examined the sequences required in vivo to promote transcription of a cell cycle-regulated human H4 histone gene. Deletion mutants of the 5' flanking region were assayed in mouse cells or fused with the chloramphenicol acetyltransferase (CAT) gene for assay in HeLa cells. The functional limits of the regulatory sequences were shown to extend at least 6.5 kilobases (kb) upstream. Sequences sufficient for correctly initiated transcription were found in the 70 base pairs (bp) immediately 5' to the cap site. A proximal element located 200-400 bp upstream increased the level of transcription several times above the basal level, although not to maximal levels. Maximal levels of expression were achieved with 6.5 kb of 5' flanking sequence adjacent to the proximal promoter sequences or when a distal enhancer element with both position- and orientation-independent function was moved proximal to the promoter. Our results indicate that a series of 5' cis-acting sequences are functionally related to the fidelity and level of expression of this human H4 histone gene.

Animals↗
PubMed1985

Hunter syndrome among Ashkenazi Jews in Israel; evidence for prenatal selection favoring the Hunter allele.

Analysis of Ashkenazi families with Hunter patients in Israel demonstrated the complete absence of new mutations among the probands' mothers. Furthermore, in these families a significant deviation of the segregation ratio between the Hunter gene and the normal allele was demonstrated among offspring of heterozygous mothers or siblings of affected children. This may be due to pre- or postzygotic prenatal selection, favoring the X chromosome carrying the Hunter gene among Ashkenazi Jews.

Alleles↗
PubMed1984

ABO incompatibility and reproductive failure. I. Prenatal selection.

An analysis of previous spontaneous abortions and the frequencies of blood-group combinations in mother-child pairs was carried out in 500 gravidae. The rate of previous spontaneous abortions in blood-group-O women whose latest child has blood group B is significantly higher than in all other women. On the other hand, the combination mother B/child AB is rarer than expected, but no increase in the rate of previous spontaneous abortions is obvious among these women. These discrepancies are interpreted as an indication that prenatal selection associated with ABO incompatibility may operate at various stages from fertilization through pregnancy, and that different incompatible combinations may be subject to selection at different stages.

ABO Blood-Group System↗
PubMed1982

The genetic analysis of monilethrix in a large inbred kindred.

The gene for monilethrix was segregating in a large inbred kindred. Pedigree analysis reaffirms an autosomal dominant mode of inheritance. Expressivity appears equally variable within and between sibships while penetrance, in contrast to previous studies, seems to be complete.

Consanguinity↗
PubMed1981

The genetics of the aryl sulfatase A locus.

A genetic analysis was performed in an isolate in which metachromatic leukodystrophy (MLD) and aryl sulfatase A (ASA) pseudodeficiency are relatively frequent. The frequency of matings at risk and the frequency of ASA pseudodeficiency among parents of MLD patients are compatible with allelism between the gene determining MLD and the gene determining ASA pseudodeficiency. Two independent pedigrees including MLD patients and ASA-deficient healthy individuals also fit the model of allelism.

Alleles↗