Gene dosage of the apolipoprotein E (APOE) epsilon 4 allele is a major risk factor for familial Alzheimer disease (AD) of late onset (after age 60). Here we studied a large series of 115 AD case subjects and 243 controls as well as 150 affected and 197 unaffected members of 66 AD families. Our data demonstrate a protective effect of the epsilon 2 allele, in addition to the dose effect of the epsilon 4 allele in sporadic AD. Although a substantial proportion (65%) of AD is attributable to the presence of epsilon 4 alleles, risk of AD is lowest in subjects with the epsilon 2/epsilon 3 genotype, with an additional 23% of AD attributable to the absence of an epsilon 2 allele. The opposite actions of the epsilon 2 and epsilon 4 alleles further support the direct involvement of APOE in the pathogenesis of AD.
P0, a major structural protein of peripheral myelin, is a homophilic adhesion molecule and maps to chromosome 1q22-q23, in the region of the locus for Charcot-Marie-Tooth neuropathy type 1B (CMT1B). We have investigated P0 as a candidate gene in two pedigrees with CMT1B and found point mutations which are completely linked with the disease (Z = 5.5, theta = 0). The mutations, glutamate substitution for lysine 96 or aspartate 90, are located in the extracellular domain, which plays a significant role in myelin membrane adhesion. Individuals with CMT1B are heterozygous for the normal allele and the mutant allele. Our results indicate that P0 is a gene responsible for CMT1B.
These results suggest that subtle subclinical changes in motor function are present in presymptomatic individuals who have inherited the HD allele.
SUMMARY A written questionnaire suitable for obtaining comprehensive genetic family data was developed. The questionnaire was designed to solicit information on the name, date of birth, sex, health problems, date of death (if deceased), spouse, abortions, stillbirths, and offspring of the patient plus first, second, and some third degree relatives of the patient.The questionnaire was evaluated for its effectiveness in obtaining an accurate and complete family history. During the first phase, 77 completed questionnaires were continuously assessed, and the questionnaire was modified until the present version evolved. Using the present version, 60 completed questionnaires disclosed only 15 problems, 10 of them minor.The questionnaire was also designed in conjunction with a computer programme developed for the entry of pedigree data. This programme is part of the computer system, MEGADATS, which is used for the acquisition, storage, and manipulation of genetic family data.The questionnaire offers these advantages over the pedigree obtained at the time of the clinic visit: (1) permits consultation with other family members, (2) saves clinic time, (3) gives prior knowledge of reason for clinic appointment, (4) anamnestic infallibility, (5) time is available to check for family record linkage, (6) computer adaptability for entering pedigree data, and (7) basic format can be modified easily. A modified sample questionnaire is presented in the Appendix.As the demand for genetic counselling services increases, more efficient methods to ensure the accurate and complete acquisition of genetic family data in the easiest possible way must be developed. Also, as computer facilities are being used more frequently to help expedite the processing of data, new methods must take into account the restrictions placed upon data collection so they will be in a format suitable for ease of entry into the computer system. The development and use of a written family history questionnaire which was designed in conjunction with an interactive computer programme developed to enter family data, code the data, and draw a family pedigree represents one method of facilitating the collection of family data.In this paper we discuss the design of the questionnaire, its use by the patients and clinical personnel in the
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.