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Biomedical subjects

M H Skolnick

Publications and source records attributed to M H Skolnick.

At least 127 records · Page 7Linked to original sources
PubMed1983

A model for restriction fragment length distributions.

We develop here a model for restriction fragment length distributions based on DNA dimer frequencies in humans. Mean fragment lengths are computed for known restriction enzymes. This model is tested using data from the hybridization of a series of arbitrary single-copy DNA probes screened with a set of restriction enzymes. The fit to the model appears good. We apply the model to the problem of how much DNA is scanned by a set of enzymes. This result is then further applied to optimizing the search for insertion/deletion DNA-polymorphisms.

Base Sequence↗
PubMed1982

Iron overload in hereditary spherocytosis: association with HLA-linked hemochromatosis.

Heavy iron loading is a rare clinical finding in patients with hereditary spherocytosis. A pedigree was studied in which the proband, a 38-year-old man, had both hereditary spherocytosis and overt hemochromatosis. He had never received blood transfusions. The 8-year-old son of the proband also had hereditary spherocytosis and mildly increased iron stores. The 39-year-old brother of the proband did not have spherocytosis but did have overt hemochromatosis. Since hemochromatosis is transmitted as an HLA-linked autosomal recessive disorder, HLA haplotypes serve as markers of hemochromatosis alleles. In this pedigree only individuals with two hemochromatosis alleles (homozygosity) had heavy iron loads, whether hereditary spherocytosis was present or not. The presence of hereditary spherocytosis may have contributed to the magnitude of the iron loading but was not a major factor. Our findings suggest that nontransfusional hemochromatosis found in association with hereditary spherocytosis is due primarily to homozygosity for hemochromatosis.

Adult↗
PubMed1982

Hereditary hemochromatosis. Analysis of laboratory expression of the disease by genotype in 18 pedigrees.

Tight linkage between the hemochromatosis locus and the HLA region permits determination of genotype in members of hemochromatosis pedigrees. To determine if simple laboratory measures of iron metabolism could predict the affected genotype without the need for HLA typing, we studied seven measures of iron metabolism: serum iron concentration, total iron-binding capacity, per cent saturation of transferrin, serum ferritin concentration, deferoxamine-induced urinary iron excretion and hepatic iron concentration evaluated by both chemical and histological methods. Discriminant analysis showed a per cent saturation of transferrin above 62% to be the best simply-measured indicator of the affected genotype: homozygosity is accurately predicted in 92% of the cases. The logarithmic transform of serum ferritin concentration was only 71% accurate. Pedigree analysis estimated the frequency of the hemochromatosis gene at 0.069 +/- 0.020 with a recombination probability of 0.015 +/- 0.015 with the HLA region. This corresponds to a heterozygote frequency of 0.13 and a disease frequency of 0.005.

Age Factors↗
PubMed1981

Coincidental nontransfusional iron overload and thalassemia minor: association with HLA-linked hemochromatosis.

A pedigree was studied in which five individuals with beta-thalassemia minor were found to have nontransfusional hemochromatosis. Three were children under the age of 10 and two were young male adults, ages 28 and 33. A 5-yr-old child without evidence of thalassemia also had hemochromatosis. Since hemochromatosis is transmitted as an HLA-linked autosomal recessive disorder, HLA haplotypes serve as markers of hemochromatosis alleles. In this pedigree, five identifiable HLA haplotypes were associated with hemochromatosis alleles. Only individuals with two hemochromatosis alleles (homozygosity) had heavy iron loads, whether beta-thalassemia minor was present or not. Individuals with beta-thalassemia minor but without a hemochromatosis allele had normal transferrin saturation. A 65-yr-old man with beta-thalassemia minor and a single hemochromatosis allele had only a minimally elevated transferrin saturation (54%). The presence of beta-thalassemia minor did not appear to accentuate the degree of iron loading expected in individuals homozygous or heterozygous for hemochromatosis alleles. Our findings suggest that nontransfusional hemochromatosis found in association with beta-thalassemia minor is due primarily to homozygosity for hemochromatosis.

Adolescent↗
PubMed1980

Analysis of a large pedigree with elliptocytosis, multiple lipomatosis, and biological false-positive serological test for syphilis.

Elliptocytosis, multiple lipomatosis, and biological false-postive serological test for syphilis (BFPSTS) were found in a single individual. One hundred eighty relatives were tested for the three diseases: 74 were typed for seven blood group antigens, and 58 were typed for four electrophoretic enzyme markers. Likelihood analysis of the pedigree data confirmed independent dominant inheritance for elliptocytosis and lipomatosis. BFPSTS appears dominant, but the analysis was inconclusive. No linkages were found between any disease gene and any marker gene. Two female pedigree members with BFPSTS developed systemic lupus erythematosus, a finding in agreement with the previously described association. The analysis did not lead to any conclusions about the causal relationship between the two traits.

Adult↗
PubMed1980

Genetic mapping of the hemochromatosis locus on chromosome six.

The purpose of this paper is to report a pedigree with hereditary hemochromatosis in which a recombination between the HLA-A and B loci occurred. Both the maternal and paternal HLA-A3, B7 haplotypes were carrying an allele for hemochromatosis. The A3, B12 haplotype of the proband was a recombinant of the maternal A3, B7 and A28, B12 haplotypes. The hemochromatosis locus segregated with the HLA-A locus and not with the HLA-B locus. Thus, the hemochromatosis locus maps in close proximity to the HLA-A locus.

Adult↗
PubMed1980

Association of HLA-linked hemochromatosis with idiopathic refractory sideroblastic anemia.

Five of seven patients with idiopathic refractory sideroblastic anemia carried an HLA-A3 alloantigen (relative risk, 7.3; P = 0.02). The significance of this association was strengthened by study of two pedigrees. An abnormality in iron metabolism was found in two siblings who had an HLA-A3,B14 haplotype in common with the first proband. A second proband with idiopathic refractory sideroblastic anemia had clinically manifest hemochromatosis. His brother had clinically manifest hemochromatosis but not sideroblastic anemia. This proband and his brother shared only the HLA-A3,B12 haplotype. Our findings infer that patients with idiopathic refractory sideroblastic anemia carry a single allele for hemochromatosis, that this allele accounts for the increased iron loading in this form of anemia, and that clinically manifest hemochromatosis may develop in an occasional patient with only one allele for hemochromatosis in the presence of the sideroblastic factor.

Adult↗
PubMed1980

Homozygosity for hemochromatosis: clinical manifestations.

We identified 35 homozygotes for hemochromatosis through pedigree studies. Thirteen were asymptomatic. Arthropathy was present in 20, hepatomegaly in 19, transaminasemia in 16, skin pigmentation in 15, splenomegaly in 14, cirrhosis in 14, hypogonadism in six, and diabetes in two. No homozygote was in congestive failure. Only one had the triad of hepatomegaly, hyperpigmentation, and diabetes. Serum iron was increased in 30 of 35, transferrin saturation was increased in all 35, serum ferritin in 23 of 32, urinary iron excretion after deferoxamine in 28 of 33, hepatic parenchymal cell stainable iron in 32 of 33, and hepatic iron in 27 of 27. Iron loading was 2.7 times greater in men than in women. No female had hepatic cirrhosis. Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy. Clinical diagnosis of early hemochromatosis is difficult. Persons with unexplained elevation of transferrin saturation should be studied for hemochromatosis.

Adolescent↗
PubMed1980

Breast cancer and reproductive history from genealogical data.

With the use of data from the Utah State Cancer Registry and Utah genealogical data, an analysis of 236 breast cancer patients and 937 controls matched on year of birth showed that a late age at the birth of the first child was most strongly associated with incidence of breast cancer (relative odds = 2.0; P less than 0.001). A strong interaction was found between age at first delivery (AFD) and age at last delivery (ALD). The association of AFD with breast cancer incidence was strongest for women with an ALD before 35 years of age even after adjustment for partly (relative odds = 4.1; P less than 0.001). Decreased parity was not significantly associated with breast cancer.

Adult↗
PubMed1979

Comparison of digital boundary detection and semi-automated analysis of left ventricular cine angiograms.

A technique has been developed to analyze automatically 35 mm left ventricular cine angiograms with an image dissector and digital computer. The analysis procedure detected the ventricular boundary and aortic valve position, then calculated the projected left ventricular area and estimated volume, and performed a polar wall motion analysis as a function of time. The automated method was compared to a semi-automated method using a technician-operated electronic cursor linked to a mini-computer. The two methods were used to analyze a set of idealized ventricular models as well as normal and abnormal angiographic data. The volumetric and wall motion data for the idealized models calculated by the two methods were equivalent (r greater than 0.99). Volumetric analysis of the patients' ventriculograms produced correlation coefficients of 0.88-0.99. Corresponding wall motion data produced correlation coefficients of 0.72-0.94. The time necessary to analyze 30 frames of cine ventriculogram was approximately 30 minutes for each method.

Aged↗
PubMed1978

Ancestral inference. I. The problem and the method.

A method for inferring the ancestral genotypes for the founders of a population is developed. This method uses the algorithms for the computation of probabilities on pedigrees of arbitrary complexity, developed by Cannings et al. (1978) and implemented by Thompson (1977b). When characteristics are simply determined by underlying genotypes the inference problem is simplified, and larger and more complex pedigrees may therefore be analysed. The problem of estimating the allele frequencies to be used in computing prior genotype probabilities for those founders on whom a likelihood function is not required is discussed. The same method allows us to compute extinction probabilities for any combination of original founder genes; these probabilities are interesting parameters of pedigree structure, which, since they relate to the actual genes present in a population, help to provide a clearer understanding of observed distributions of autosomal traits.

Gene Frequency↗