Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals.

Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

http://science.sciencemag.org/content/sci/235/4791/885.full.pdf

The genetic defect causing familial Alzheimer's disease maps on chromosome 21

An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus.

Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) are human X-linked muscle-wasting disorders that have been localized to the band Xp21 by genetic linkage analysis1–9 and cytologically detectable abnormalities10–12. A cloned DNA segment, DXS164 (or pERT87), has been shown to detect deletions in the DNA of unrelated DMD and BMD males13–15. Here we present the nucleotide sequence of two highly conserved DNA fragments from the DXS164 locus and their homologous sequences from the mouse X chromosome. One of the human conserved segments hybridized to a large transcript in RNA isolated from human fetal skeletal muscle and was used to isolate cDNA clones which cover approximately 10% of this transcript. The cDNA clones map to Xp21 and hybridize with a minimum of eight small regions that span 130 kilobases (kb) of the DXS164 locus. These expressed sequences are candidates for portions of the gene responsible for both DMD and BMD.

Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene

A pedigree study shows close linkage of bipolar affective illness (manic depression) to the X-chromosome markers colour blindness and glucose-6-phosphate dehydrogenase deficiency. The maximum lod score ranges from 7.52 (assuming homogeneity) to 9.17 (assuming heterogeneity); that is, the odds in favour of linkage range between 3×107 to 1 and 109 to 1. These results provide confirmation that a major psychiatric disorder can be caused by a single genetic defect. As a possible first step in characterizing the primary genetic abnormality, this finding may have important implications for the aetiology, nosology, pathophysiology and, possibly, prevention and treatment of bipolar affective disorder. It also provides a means for identifying and characterizing homogeneous populations of patients and may help in clarifying aetiological heterogeneity.

P.N. Goodfellow

Papers

Report of the committee on the genetic constitution of the X and Y chromosomes