Exclusion mapping of familial Alzheimer disease (FAD) in the Volga Germans

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134703

Levy-Lehad, E; Wijsman, E M ^[1]; Bird, T D ^[2]

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1. Univ. of Washington, Seattle, WA (United States)
2. Veterans` Affairs Medical Center, Seattle, WA (United States); and others

The Volga Germans (VG) are an ethnically distinct group of 8 families in whom early-onset (mean age-of-onset <60 years) FAD segregates as an autosomal dominant trait, probably due to a founder effect. Known FAD loci are a chromosome 14q24.3 locus for which the majority of early-onset FAD families show linkage, and the ApoE4 allele of the apolipoprotein E (ApoE) gene on chromosome 19q11.3. Linkage of VG FAD to markers on chromosomes 14, 21 and 19 has been excluded, and no APP mutations were found in affected VG subjects. The VG have an increased frequency of ApoE4 but do not show an association of FAD with the ApoE4 allele. In contrast to late-onset FAD families, ApoE4 does not modify age-of-onset in the VG: mean age-of-onset is 62.2{plus_minus}10.0 years for affected individuals with no ApoE4 alleles, 62.0{plus_minus}6.0 for affecteds homozygous for ApoE4. Therefore FAD in the VG group is caused by a locus which is as yet unidentified. To map this locus we have undertaken a genome-side search using short-tandem-repeat (STRP) markers evenly spaced (about every 20 cM) on all the autosomes. We have analyzed over 30 RFLPs and over 100 STRP markers. Approximately 50% of the genome has been excluded. An exclusion map, using the EXCLUDE program, is continuously updated to indicate regions of high likelihood for linkage.

• OSTI ID: 134703
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
AGE DEPENDENCE
APOLIPOPROTEINS
BIOLOGICAL MARKERS
DOMINANT MUTATIONS
E CODES
FEDERAL REPUBLIC OF GERMANY
GENE MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 14
HUMAN CHROMOSOME 19
HUMAN CHROMOSOME 21
MENTAL DISORDERS
NERVOUS SYSTEM DISEASES
PATIENTS
RFLPS
STATISTICS