Publication Date:
1987-11-13
Description:
The discovery of D4S10, an anonymous DNA marker genetically linked to Huntington's disease (HD), introduced the capacity for limited presymptomatic diagnosis in this late-onset neurodegenerative disorder and raised the hope of cloning and characterizing the defect based on its chromosomal location. Progress on both fronts has been limited by the absence of additional DNA markers closer to the HD gene. An anonymous DNA locus, D4S43, has now been found that shows extremely tight linkage to HD. Like the disease gene, D4S43 is located in the most distal region of the chromosome 4 short arm, flanked by D4S10 and the telomere. In three extended HD kindreds, D4S43 displays no recombination with HD, placing it within 0 to 1.5 centimorgans of the genetic defect. Expansion of the D4S43 region to include 108 kilobases of cloned DNA has allowed identification of eight restriction fragment length polymorphisms and at least two independent coding segments. In the absence of crossovers, these genes must be considered candidates for the site of the HD defect, although the D4S43 restriction fragment length polymorphisms do not display linkage disequilibrium with the disease gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilliam, T C -- Bucan, M -- MacDonald, M E -- Zimmer, M -- Haines, J L -- Cheng, S V -- Pohl, T M -- Meyers, R H -- Whaley, W L -- Allitto, B A -- NS16367/NS/NINDS NIH HHS/ -- NS20012/NS/NINDS NIH HHS/ -- NS22031/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1987 Nov 13;238(4829):950-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurogenetics Laboratory, Massachusetts General Hospital, Boston.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2890209" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
*Chromosomes, Human, Pair 4
;
Cloning, Molecular
;
Cosmids
;
*Genes
;
*Genetic Linkage
;
Humans
;
Huntington Disease/*genetics
;
Polymorphism, Restriction Fragment Length
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
