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M C King

Publications and source records attributed to M C King.

At least 145 records · Page 8Linked to original sources
PubMed1986

Genetic analysis of cystic fibrosis: linkage of DNA and classical markers in multiplex families.

Linkage of cystic fibrosis (CF) to DNA and classical markers was studied in 36 families of two or three generations with at least two living affected children. Among the 79 affected children, no recombinants were detected between the disease and the markers MET and pJ3.11, previously shown to be linked to CF. No linkage between the human trypsin gene family (which appears to include at least 10 members) and CF was found, although not all genes of the trypsin family have been screened yet. In one of the CF families, recombination between MET and pJ3.11 was detected in an unaffected sib. Data from our families suggest that the gene order of markers among chromosome 7q is: (7cen;p8.33)collagen(COL1A2);DOCR1-917;paraoxonase+ ++(PON);(MET-cf-J3.11);T-cell receptor beta chain (TCRB);qter. There was no evidence for (or against) either postzygotic selection or meiotic drive to explain the high frequency of CF in Caucasian populations.

Cystic Fibrosis↗
PubMed1986

Genetic interrelationship between insulin-dependent diabetes mellitus, the autoimmune thyroid diseases, and rheumatoid arthritis.

To investigate the possible coinheritance of autoimmune diseases that are associated with the same HLA antigen, we studied 70 families in which at least two siblings had either type I diabetes mellitus (IDDM), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), or a combination of these diseases. HLA-A, B, and C typing was performed on all affected sibs in one generation or more. First, we estimated by sib-pair analysis the disease allele frequency (pD) and the mode of inheritance for each disease. According to the method of ascertainment entered into the analysis, the pD for ATD ranged from .120 to .180, for an additive (dominant) mode of inheritance. For RA, the pD ranged from .254 to .341, also for additive inheritance, although recessive inheritance could not be excluded. For IDDM, the pD ranged from .336 to .337 for recessive inheritance; additive inheritance was rejected. Second, we examined the distribution of shared parental haplotypes in pairs of siblings that were discordant for their autoimmune diseases. The results suggested that the same haplotype may predispose to both IDDM and ATD, or IDDM and RA, but not to both RA and ATD. Analysis of pedigrees supported this hypothesis. In 16 families typed for HLA-DR also, the haplotype predisposing to both IDDM and ATD was assigned from pedigree information to DR3 (44%), DR4 (39%), or DR5, DR6, or DR7 (5.5% each). In some families, these haplotypes segregated over several generations with ATD only (either clinical or subclinical), suggesting that in such families, ATD was a marker for a susceptibility to IDDM. In several families, an IDDM haplotype segregated with RA but not with ATD. This suggests that ATD- and RA-associated susceptibilities to IDDM may be biologically different and thus independently increase the risk of IDDM.

Arthritis, Rheumatoid↗
PubMed1986

Detecting linkage for genetically heterogeneous diseases and detecting heterogeneity with linkage data.

Interest in searching for genetic linkage between diseases and marker loci has been greatly increased by the recent introduction of DNA polymorphisms. However, even for the most well-behaved Mendelian disorders, those with clear-cut mode of inheritance, complete penetrance, and no phenocopies, genetic heterogeneity may exist; that is, in the population there may be more than one locus that can determine the disease, and these loci may not be linked. In such cases, two questions arise: (1) What sample size is necessary to detect linkage for a genetically heterogeneous disease? (2) What sample size is necessary to detect heterogeneity given linkage between a disease and a marker locus? We have answered these questions for the most important types of matings under specified conditions: linkage phase known or unknown, number of alleles involved in the cross at the marker locus, and different numbers of affected and unaffected children. In general, the presence of heterogeneity increases the recombination value at which lod scores peak, by an amount that increases with the degree of heterogeneity. There is a corresponding increase in the number of families necessary to establish linkage. For the specific case of backcrosses between disease and marker loci with two alleles, linkage can be detected at recombination fractions up to 20% with reasonable numbers of families, even if only half the families carry the disease locus linked to the marker. The task is easier if more than two informative children are available or if phase is known. For recessive diseases, highly polymorphic markers with four different alleles in the parents greatly reduce the number of families required.

Alleles↗
PubMed1986

Polymorphisms of mitochondrially encoded proteins.

Polymorphisms of mitochondrially encoded proteins can be detected in human lymphocytes by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Using an SDS-polyacrylamide 8 M urea system, 17 mitochondrially encoded proteins are distinguishable. Three of these (ME-6, ME-8, and ME-17) were polymorphic among 92 individuals screened, and these polymorphisms are reported here for the first time. With SDS-polyacrylamide electrophoresis without urea, 18 mitochondrial proteins are detectable. One of these (MV-1) varied in two of 31 individuals tested. This polymorphism has been identified previously in HeLa cells. Maternal inheritance of the ME-8 polymorphism was demonstrated by three informative families.

DNA, Mitochondrial↗
PubMed1985

Risk of breast cancer to relatives of young breast cancer patients.

Breast cancer risk among sisters and mothers of a population-based series of 1,137 breast cancer patients diagnosed in Metropolitan Detroit before the age of 55 years was compared with risk to the same relatives of 1,001 age-matched, population-based controls. After adjusting for age of the relative, for age of the case or control, and for race, the odds ratio for breast cancer for women with affected sisters was 2.2; for women with affected daughters, 3.2; and for women with affected mothers and sisters, 9.9. Breast cancer in aunts had no independent influence on risk. Among white women, cumulative risk of breast cancer before the age of 50 years was approximately 1% for relatives of controls, 3% for sisters of older cases, but about 17% for women either with sisters diagnosed before the age of 40 years or with affected sisters and mothers. Sisters of the older patients had a 13% risk of breast cancer by 70 years of age, compared to 5% for sisters of controls. White women with affected mothers and sisters were at 50% risk by 65 years of age. This study identifies the criteria for women who could receive particular benefit from screening for breast cancer.

Adult↗
PubMed1984

Risk factors for benign breast disease: a case-control study of discordant twins.

The influences of potential risk factors for benign breast disease were assessed using women twins in a matched pair design. Two groups of cases from the Kaiser-Permanente Twin Registry were considered: 1) 90 pairs of female twins in which one twin reported a history of benign breast disease confirmed by biopsy and her twin reported no history of benign breast disease, and 2) 48 pairs of female twins in which the case had clinically diagnosed fibrocystic benign breast disease and her twin was free of disease at examination and reported no history of the disease. Results were similar in these two samples. A significant positive association was found between benign breast disease and coffee consumption. Oral contraceptive use and greater body mass were inversely associated with benign breast disease after controlling for possible confounding variables by matched-pairs multiple logistic analysis. All associations were stronger for monozygotic than for dizygotic pairs. Twin pairs discordant for disease provide an excellent sample in which to assess the importance of potential risk factors while controlling for early environmental and genetic backgrounds.

Adult↗
PubMed1984

Human genetics and human rights. Identifying the families of kidnapped children.

Between 1975 and 1983 in Argentina, at least 145 children were kidnapped with their parents or born in captivity to imprisoned women and then separated from their mothers. The parents of these children generally remain among the missing persons. However, the grandparents of the kidnapping victims and the Argentinian government are concerned with identifying these children. Genetic analysis can aid in determining whether a child who may be among the kidnap victims is related biologically to a particular family. Laboratory analysis of genetic markers in human blood enables the calculation of an "index of grandpaternity." This index reflects the probability that a child shares genes with a specified set of grandparents because he is their grandchild compared to the probability he and they share similar genes only by chance. The most useful system for this analysis is HLA, although other genetic markers including blood groups, red cell enzymes, plasma proteins, and DNA polymorphisms can be tested to provide adequate information in families with only one or two living grandparents. This approach has been applied successfully in Argentina, with an index of grandpaternity for one family of 99.9%, based on HLA typing only.

Child↗
PubMed1983

Practical guide for estimating risk for familial breast cancer.

Life-table analysis was used to estimate the cumulative risk of breast cancer to various ages for mothers and sisters of breast cancer patients in a population-based series. These cumulative risk estimates were then used to derive a probability of breast cancer diagnosis within each decade between ages 20 and 70 for mothers and sisters, according to age of diagnosis in the patient and whether the disease was unilateral or bilateral. Risks for relatives of premenopausal patients with unilateral disease were no higher than those for relatives of postmenopausal patients. Relatives of premenopausal patients with bilateral disease had higher risk than relatives of patients with unilateral disease, irrespective of age at diagnosis in those with unilateral disease. Sisters were at higher risk than were mothers.

Actuarial Analysis↗
PubMed1983

The inheritance of immunoglobulin E: genetic linkage analysis.

Linkage analyses between 21 genetic markers including HLA-A, B, and the postulated locus for determining total serum IgE levels were done to try to clarify the inheritance of total IgE levels and to map the locus. A total of 316 individuals from five Mormon kindreds were studied, and data from an additional 204 Amish individuals from 11 families were analyzed for possible HLA linkage. Segregation analyses of both data sets did not give clear definition of the mode of inheritance of total IgE levels, but purely environmental models were rejected. Linkage analyses gave significant evidence against HLA linkage with the codominant, recessive, or dominant model of inheritance for total IgE levels. No significant evidence for linkage with any of the genetic markers was obtained. Since total serum IgE levels are correlated with allergies, understanding the genetics of total IgE levels is important to understanding the genetics of allergic disease in man.

Blood Group Antigens↗
PubMed1983

Hodgkin's disease susceptibility: linkage to the HLA locus demonstrated by a new concordance method.

The role of genetic susceptibility in the pathogenesis of Hodgkin's Disease has been considered relatively minor because of the rarity of familial disease, the absence of an identified pattern of inheritance, and the weakness of HLA associations in population studies. The availability of four prospectively ascertained HD families permitted reappraisal of the cosegregation of HLA and HD susceptibility by a new extended concordance analysis method. HLA haplotype concordance among patients was greater than that expected by chance alone for our four families (P less than 0.022) and also for these in combination with twelve informative families in the literature (P less than 0.0015). This study thus provides a new method, based on genotype concordance of affected relatives, for assessing linkage of HLA and disease susceptibility, and new evidence for the genetic control of susceptibility to HD. The model presented, as well as alternative and more complex models, points to the existence of an HD susceptibility gene in or near the HLA region, which, in the presence of a suitable etiologic agent or additional genetic susceptibility, leads to the induction of HD.

Adult↗
PubMed1983

A memory model of sequential effects in scaling tasks.

Subjects judge successive stimuli to be overly similar in psychophysical scaling tasks. This is called assimilation. They also tend to judge each stimulus as overly different from more previous events. This is called contrast. To examine a two-stage linear model of these sequence effects, we asked subjects to judge the relative intensity of successive tones. In support of the model, responses again depended lawfully on prior events. These memory effects occur in a variety of scaling tasks and are consistent with two assumptions: (a)Successive events assimilate in memory, and (b) subjects compare each stimulus to a collection of memories of prior events to generate a response. The trial-by-trial analysis used to test the model also showed that even in magnitude-estimation studies, equal stimulus ratios do not result in equal response ratios, except on average. This article suggests that examinations of trial-by-trial performance might be useful in studying memory and judgment processes.

Discrimination Learning↗
PubMed1983

Genetic epidemiology of breast cancer and associated cancers in high-risk families. I. Segregation analysis.

Genetic and environmental hypotheses that might explain the patterns of occurrence of breast cancer and associated cancers in 18 large families at high risk of the disease were tested with the use of segregation analysis. For 16 pedigrees, results were consistent with the hypothesis that breast cancer has a genetic etiology. In 2 other families, breast cancer appeared more likely to have an environmental origin. Breast cancer susceptibility is best explained by hypotheses that postulate autosomal dominant susceptibility alleles in 10 families with primarily premenopausal breast cancer and ovarian cancer, in 4 families with primarily postmenopausal breast cancer, and in 2 families with breast cancer, brain tumor, sarcoma, leukemia, and adrenocortical carcinoma in children and young adults. In an accompanying paper, genetic susceptibility in the first 2 groups of families is further explored with the use of linkage analysis.

Adult↗
PubMed1983

Genetic epidemiology of breast cancer and associated cancers in high-risk families. II. Linkage analysis.

Chromosomal locations of hypothetical alleles which increase susceptibility to human breast cancer in some families were investigated by genetic linkage analysis. In 7 families with primarily premenopausal breast cancer and (in 5 families) ovarian cancer, a dominant susceptibility allele may be linked to the genetic marker glutamicpyruvic transaminase or alanine aminotransferase (GPT; lod score 1.95 at zero recombination). The most positive lod score for linkage to a recessive susceptibility allele was for acid phosphatase (ACP; lod score 0.78 at 40% recombination), but ACP was informative in ony 1 family. In 3 families with primarily postmenopausal breast cancer, none of 21 genetic markers provided any evidence for linkage to either dominant or recessive susceptibility alleles. In the families with the possible GPT linkage, women who carry the hypothetical susceptibility allele would be at high risk of breast cancer, whereas their relatives who do not carry that allele would have no increased risk. GPT genotype is not associated with breast cancer risk in the general population, so GPT linkage cannot be used as a screening test for breast cancer.

Alleles↗
PubMed1981

Problem-solving task performance in brain-damaged subjects.

Investigated the relationship between the Halstead Category Test and the Wisconsin Card Sorting Test. A correlational analysis revealed a statistically significant but modest relationship between the two variables in separate samples of brain-damaged and non-brain-damaged individuals (N = 156). Thus, in spite of the apparent similarity of the two measures, their relationship is not sufficiently close to suggest that in fact they are measuring the same abilities. However, the combination of hit rates of the two measures and the high base rate of brain dysfunction in the present sample yielded good diagnostic accuracy for decisions with regard to the presence of brain damage.

Adult↗
PubMed1981

Effects of non-focal brain dysfunction on visual memory.

Investigated the effects of non-focal brain damage on visual memory abilities with a sample of 114 Ss with confirmed brain-dysfunction and 71 controls who completed the Rey-Osterrieth Complex Figure Test. In contrast, to the findings of earlier studies of patients with focal brain-damage, right-hemisphere lesioned Ss could not be discriminated from left-hemisphere lesioned Ss on the basis of impaired visual recall. All three brain-damaged groups, however, performed more poorly than the control group in both the copy and recall phases of the task. Age and intelligence also were found to be related inversely to task performance. Implications of these data for clinical neuropsychological assessment are discussed.

Adult↗