A large family with Charcot‐Marie‐Tooth disease, showing a probable X‐linked incomplete dominant inheritance, was studied by linkage analysis. Results, obtained by the use of X chromosome specific DNA probes of known regional location, suggest that the disease locus is linked to the DXYS1 locus (ž=2.59 at θ= 0.00) and to the DXS14 locus and, places the disease locus between the DXYS1 locus and the DXS14 locus, near the centromere of the X chromosome. Together with the published data, a distance of 13 cM (ž= 6.95) was assessed between the disease locus and the DXYS1 locus.
Data on 72 families with multiple cases of leprosy were analyzed for a susceptibility gene linked to the HLA loci. We conducted segregation analysis with the program POINTER and identity of HLA types by descent analysis to determine the most likely mode of inheritance. We then conducted linkage analysis with the program LINKAS, first assuming linkage equilibrium and then allowing for linkage disequilibrium and etiological heterogeneity. Segregation results suggest a recessive mode of inheritance, especially for the tuberculoid forms of leprosy. The linkage results, limited to tuberculoid forms and assuming a recessive model, suggest a hypothesis of loose linkage with no unlinked locus. When an additive model is assumed, the best fit is obtained with a hypothesis of complete linkage (Θ = 0.0) with heterogeneity. We currently favor the additive model as the more plausible one.
Risk factors such as maternal age, parity, previous siblings' death, inbreeding of parents, birth weight, birth length were examined in a population‐based prospective study in four population groups at different levels of urbanization in and round Lahore, Pakistan. From September 1984 to March 1995, 2967 full‐term, single born infants were followed from the 5th month of gestation to 12 months of age. Logistic regression analysis showed a significant relative risk (RR) of infant death associated with parents' consanguinity (RR = 1.8), birth weight (RR = 1.8) and elder siblings' death (RR = 1.7). The risk attributed to these factors was 28, 17 and 25%, respectively. The number of lethal equivalents per gamete is about one. The B/A ratio 10.36 suggests that the genetic load is likely to be mutational. In countries like Pakistan, where consanguinity is favourably practiced, a substantial proportion of infant deaths may be prevented by cessation of such marriages. The implications of this finding for the Pakistani community are discussed.
Insulin release and sensitivity were estimated from glucose and insulin curves obtained at a glucose infusion test performed on altogether 601 subjects belonging to 155 nuclear families. Ascertainment was through one of the parents, and 96 of the probands had diabetes with clinical onset after the age of 30 years, while 59 were healthy subjects. Three variables obtained by a computer model were analysed, i.e. the glucose regulation of insulin release by a direct stimulatory event (KI) and time‐dependent modulatory events (KP) as well as insulin sensitivity (KG). Complex segregation analysis revealed that the variables are genetically regulated, but there was no evidence for a major locus. The children of the diabetics did not differ from those of the non‐diabetics as far as insulin release is concerned.
