Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients

• Published in: American journal of human genetics Vol. 57; no. 1; pp. 40 - 48
• Main Authors: CHRISTIAN, S. L, ROBINSON, W. P, HUANG, B, MUTIRANGURA, A, LINE, M. R, NAKAO, M, SURTI, U, CHAKRAVARTI, A, LEDBETTER, D. H
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01-07-1995
• Subjects: Angelman Syndrome - genetics; Angelman's syndrome; Base Sequence; Biological and medical sciences; chromosome 15; Chromosome Mapping; Chromosomes, Human, Pair 15 - genetics; Complex syndromes; deletion; DNA, Satellite - analysis; Female; genetic mapping; Genetic Markers; Humans; Lod Score; man; Medical genetics; Medical sciences; mental retardation; Molecular Sequence Data; Ovarian Neoplasms - genetics; Polymerase Chain Reaction; Polymorphism, Genetic; Prader-Willi syndrome; Prader-Willi Syndrome - genetics; Sequence Deletion; Teratoma - genetics; yeast artificial chromosomes; Chromosomal aberration; Endocrinopathy; Genetic mapping; Human; Breakpoint; Nervous system diseases; Genetic marker; Repeated sequence; Diabetes mellitus; Diseases of the osteoarticular system; Happy puppet syndrome; Congenital disease; Cerebral disorder; Target tissue resistance; Abnormal D15 chromosome; Centromere; Malformation; Central nervous system disease; Deletion; Abnormal chromosome; Genetics; Complex syndrome; Prader Labhart Willi syndrome
• ISSN: 0002-9297; 1537-6605

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11-q13. Approximately 70% of these patients have a large deletion of approximately 4 Mb extending from D15S9 (ML34) through D15S12 (IR10). To further characterize the deletion breakpoints proximal to D15S9, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated from YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 markers on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these markers (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542.