Molecular dissection of a contiguous gene syndrome: Frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated island in the Miller-Dieker chromosome region

Journal Article · Sat Jul 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.13.5136· OSTI ID:5227584

Ledbetter, D H; Ledbetter, S A; vanTuinen, P; Summers, K M; Robinson, T J; Nakamura, Yusuke; Wolff, R; White, R; Barker, D F; Wallace, M R; Collins, F S; Dobyns, W B ^[1]

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1. Baylor College of Medicine, Houston, TX (USA)

The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be <15 kb apart. Three overlapping cosmids spanning >100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region.

• OSTI ID: 5227584
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:13; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHROMOSOMAL ABERRATIONS
GENETIC MAPPING
HEREDITARY DISEASES
MOLECULAR BIOLOGY
BIOLOGICAL EVOLUTION
BIOLOGICAL MARKERS
DNA
DNA HYBRIDIZATION
DNA SEQUENCING
ELECTROPHORESIS
HETEROCHROMOSOMES
HYBRIDIZATION
KARYOTYPE
MAN
METHYLATION
MICE
PHOSPHORUS 32
RFLPS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHEMICAL REACTIONS
CHROMOSOMES
DAYS LIVING RADIOISOTOPES
DISEASES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAPPING
MUTATIONS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550401* - Genetics- Tracer Techniques