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C T Falk

Publications and source records attributed to C T Falk.

At least 37 records · Page 2Linked to original sources
PubMed1987

Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations.

An alternative to Woolf's (1955) relative risk (RR) statistic is proposed for use in calculating the risk of disease in the presence of particular antigens or phenotypes. This alternative uses, as the control sample, the parental antigens or haplotypes not present in the affected child. The formulation of a haplotype relative risk (HRR) thus eliminates the problems of sampling from the same homogeneous population to form both the disease sample and an appropriate control. We show that, in families selected through a single affected individual, where transmission of the four parental haplotypes can be followed unambiguously, the mathematical expectation of the HRR is identical to that of the RR. Since the sample formed from the 'non-affected' parental haplotypes is clearly from the same population as the disease sample, the HRR thus provides a reliable alternative to the RR. A further advantage obtains when family data are being collected as part of a study since the control sample is then automatically contained in the family material. Data from studies of patients with insulin dependent diabetes mellitus (IDDM) are used to obtain an estimate of the risk to those with HLA antigens or phenotypes associated with IDDM using the HRR statistic. A comparison of the HRR's and RR's for these data is also presented.

Diabetes Mellitus, Type 1↗
PubMed1986

Use of molecular haplotypes specific for the human pro alpha 2(I) collagen gene in linkage analysis of the mild autosomal dominant forms of osteogenesis imperfecta.

Autosomal dominant osteogenesis imperfecta (OI) is a heterogeneous group of disorders. Molecular haplotypes associated with the pro alpha 2(I) gene of human type I procollagen were used for genetic linkage studies in a group of 10 families with OI. The clinical phenotypes of the families studied were those of OI type I and OI type IV. Evidence for linkage was highly suggestive in the four families with OI type IV (Z = 3.91 for theta = 0). In contrast, little or no indication for linkage was found in the six families with OI type I (Z = .055 for theta = .415). Heterogeneity between the two groups of families was highly significant (chi 2 = 11.14, P = .0008), suggesting that at least two separate gene defects may be the cause of the autosomal dominant forms of OI.

Alleles↗
PubMed1984

Estimating the recombination frequency for the PTC-Kell linkage.

Two data sets are analyzed for linkage between the PTC and Kell blood group loci. The original report of close linkage for these loci was that of Conneally et al. (1976), where the maximum likelihood estimate of theta was 0.05. These two new data sets give a combined maximum likelihood estimate of theta m = f = 0.28. Estimating the recombination frequency for the sexes separately gave theta m = 0.29, theta f = 0.23. The combined maximum likelihood estimate over all published data sets including this report is theta m = f = 0.14, Zmax = 8.94. There is statistically significant evidence of heterogeneity among the published studies.

Blood Group Antigens↗
PubMed1984

A two-susceptibility-allele model for genetic diseases and associated marker loci: differences and similarities to a one-s-allele model.

A model for genetic diseases and associated markers is defined where two distinct susceptibility alleles are possible, each associated with a different marker allele. Marker genotype distributions in a disease population are then expressed in terms of haplotype frequencies and penetrance parameters. It is shown that, if the heterozygote with two different disease alleles has a higher penetrance than the two disease homogzygotes, the observed to 'Hardy-Weinberg-expected' ratio of associated marker genotypes (the alpha/beta ratio of Falk, Mendell & Rubinstein, 1983) will always be greater than or equal to one. When all disease penetrances are equal, the model becomes indistinguishable from a recessive one-s-allele model with alpha/beta = 1. Application of these observations to several data sets for insulin dependent diabetes mellitus suggests the possibility that different marker genotype distributions in different samples may be due to different penetrances of the disease genotypes in the samples. If a particular environment causes the heterozygote disease genotype (with two different disease alleles) to have the highest penetrance, the marker genotype distribution would be compatible with the 2-s-allele model. In other environments where the three disease genotypes have essentially equal penetrances, the marker distribution would be compatible with the 1-s-allele model.

Alleles↗
PubMed1984

Genetic Analysis Workshop II: summary.

The second Genetic Analysis Workshop was held October 30, 1983, at the American society of Human Genetics meetings in Norfolk, Virginia. Ten groups of investigators analyzed three sets of pedigrees generated by computer simulation. A summary of the workshop is presented. In this overall description by the workshop organizers, the rationale for the choice of problems and the characteristics of the three data sets are discussed, and the ten analyses are briefly summarized and compared. Following this general summary are brief descriptions of the analyses of each group of workshop participants, in alphabetical order by senior author.

Adult↗
PubMed1983

Effect of population associations and reduced penetrance on observed and expected genotype frequencies in a simple genetic model: application to HLA and insulin dependent diabetes mellitus.

The observed and Hardy--Weinberg-expected frequencies for (HLA) marker heterozygotes in a disease population are calculated where it is assumed that the disease is caused by either homozygosity or heterozygosity (with reduced pentrance) for a disease susceptibility allele at a disease locus, that allele being positively associated with both of the relevant alleles at the marker locus (the single susceptibility allele model of Svejgaard & Ryder, 1981). It is shown that the observed frequency is always less than or equal to the H-W expectation, with the (observed/expected) ratio decreasing as the degree of dominance increases.

Alleles↗
PubMed1980

The effect of association of genetic factors on relative risk.

We have examined the numerical properties of relative risk (RR) estimates under the conditions of gene frequency and genetic association (delta) that generally obtain for the different HLA loci. It is found that significant RR may be created solely by the existence of positive delta between the disease susceptibility gene and a specific allele at the marker (e.g. HLA) locus. It is shown further, that the value of RR is strongly affected by the gene frequencies and not only by the corresponding delta. If positive delta exists between one disease susceptibility gene and two HLA haplotypes, the RR estimates will usually be highest for the corresponding heterozygote, intermediate for the two homozygotes and lowest for the other carrier phenotypes. This model was found to be perfectly compatible with the situation encountered in the case of juvenile diabetes mellitus and shows that 'overdominance' is not required to account for the excessive RR found in some populations for certain HLA heterozygous classes.

Alleles↗