Linkage disequilibrium in the insulin gene region is related to the exact number of repeat units present at the 5{prime} flanking polymorphism

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

OSTI ID:133917

McGinnis, R E; Spielman, R S ^[1]

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1. Univ. of Pennsylvania, Philadelphia, PA (United States)

Tandem DNA repeat units (RUs) located 5{prime} to the insulin (INS) gene give rise to a {open_quotes}5{prime} flanking polymorphism{close_quotes} (5{prime}FP) with minisatellite alleles belonging to 3 size classes. The shortest or {open_quotes}class 1{close_quotes} alleles (mean length of {approximately}40 RUs) are associated with insulin-dependent diabetes mellitus (IDDM), and the 5{prime}FP is one of several INS region loci in strong linkage disequilibrium with IDDM. We have amplified class 1 alleles and have determined the exact number of RUs in individual class 1 alleles found in parents of 50 IDDM families. We also obtained INS region haplotypes by typing two loci near tyrosine hydroxylase (TH) and two loci near insulin-like growth factor II (IGF2). We obtained these results: (1) Class 1 alleles (n=101) were found at every integer length from 30 to 44 RUs, the lengths of smallest and largest class 1 alleles observed. The allele frequency distribution was trimodal with peaks at 31, 40 and 42 RUs; 18%, 34% and 48% of the alleles belonged to the three components, respectively. (2) Allelic variation at each flanking locus was highly associated with the exact number of RUs present at the 5{prime}FP. Our results suggest that creation of new 5{prime}FP or other minisatellite haplotypes may be {open_quotes}constrained{close_quotes} in that flanking alleles usually become associated with a new minisatellite length different by only one or two RUs. Furthermore, since many flanking alleles were associated with a single narrow range of class 1 integer lengths, determining exact RU length may aid in visualizing linkage disequilibrium and allelic associations involving other minisatellite loci.

• OSTI ID: 133917
• 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
BIOLOGICAL MARKERS
DIABETES MELLITUS
DNA
GENE MUTATIONS
GENES
GROWTH FACTORS
HYDROXYLASES
INSULIN
NUCLEOTIDES
PATIENTS
SIZE
STATISTICS
TYROSINE