iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://pubmed.ncbi.nlm.nih.gov/15077200
Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p - PubMed Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004 May;74(5):876-85.
doi: 10.1086/420772. Epub 2004 Apr 7.

Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p

Shenghan Chen  1 , William G Ondo, Shaoqi Rao, Lin Li, Qiuyun Chen, Qing Wang
Affiliations

Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p

Shenghan Chen et al. Am J Hum Genet. 2004 May.

Abstract

Restless legs syndrome (RLS) is a common neurological disorder that affects 5%-12% of all whites. To genetically dissect this complex disease, we characterized 15 large and extended multiplex pedigrees, consisting of 453 subjects (134 affected with RLS). A familial aggregation analysis was performed, and SAGE FCOR was used to quantify the total genetic contribution in these families. A weighted average correlation of 0.17 between first-degree relatives was obtained, and heritability was estimated to be 0.60 for all types of relative pairs, indicating that RLS is a highly heritable trait in this ascertained cohort. A genomewide linkage scan, which involved >400 10-cM-spaced markers and spanned the entire human genome, was then performed for 144 individuals in the cohort. Model-free linkage analysis identified one novel significant RLS-susceptibility locus on chromosome 9p24-22 with a multipoint nonparametric linkage (NPL) score of 3.22. Suggestive evidence of linkage was found on chromosome 3q26.31 (NPL score 2.03), chromosome 4q31.21 (NPL score 2.28), chromosome 5p13.3 (NPL score 2.68), and chromosome 6p22.3 (NPL score 2.06). Model-based linkage analysis, with the assumption of an autosomal-dominant mode of inheritance, validated the 9p24-22 linkage to RLS in two families (two-point LOD score of 3.77; multipoint LOD score of 3.91). Further fine mapping confirmed the linkage result and defined this novel RLS disease locus to a critical interval. This study establishes RLS as a highly heritable trait, identifies a novel genetic locus for RLS, and will facilitate further cloning and identification of the genes for RLS.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Genomewide NPL scan for RLS-susceptibility loci. A total of 404 microsatellite markers spanning the entire human genome were genotyped in 144 individuals from multiplex RLS families. The vertical Y-axis of each plot denotes NPL scores generated by GENEHUNTER. The X-axis represents marker map positions in cM from the telomere of the p arm of each chromosome. The horizontal solid line in each plot corresponds to an NPL score of 3.0.
Figure 2
Figure 2
Multipoint LOD-score analysis for markers at the 9p 24.2–22.3 RLS locus. Random walk analysis was done using SimWalk2. Location of marker D9S1779 is arbitrarily set at 0 cM. Other microsatellite markers are scaled on the basis of their absolute distance (in cM) from D9S1779. Multipoint LOD scores are plotted on the ordinate. The dashed line marks an LOD score of 3.0.
Figure 3
Figure 3
Haplotype analysis in kindred 40004 affected with RLS. Circles and squares denote females and males, respectively; blackened symbols indicate affected individuals; unblackened symbols indicate normal individuals; the symbol with a slash indicates a deceased individual; and symbols with a question mark indicate an individual with uncertain phenotype. Genotyping results for markers D9S1779, D9S1871, D9S2169, D9S286, D9S168, D9S268, D9S274, D9S1839, D9S162, and D9S1121 are shown under each symbol. Haplotypes were constructed on the basis of the minimum number of recombinations between markers. The disease haplotype shared by all affected individuals is denoted by the blackened vertical bar, and normal haplotype is denoted by an unblackened vertical bar. Recombination events were observed in individuals III-1, III-2, and III-3 and defined the critical RLS gene location as upward from marker D9S162.
Figure 4
Figure 4
Haplotype analysis in kindred 40015 affected with RLS. Data are shown as described in fig. 3. Two recombination events were observed, one in individual II-1 and the other in III-1. The obligate recombination in II-1 defined the RLS gene location as downward from D9S1779.
Figure 5
Figure 5
Ideogram of chromosome 9 with Geimsa banding and localization of the 9p24-22 RLS locus. The genetic map with chromosome 9p24-22 markers is shown, and the likely location of the putative RLS gene is indicated by a vertical bar (from D9S1871 to D9S1839).
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

Electronic-Database Information

    1. GENEHUNTER, http://linkage.rockefeller.edu/soft/gh/ or http://www.hgmp.mrc.ac.uk/About/Courses/2003/comp.linkage/genehunt.html
    1. Human Genome Resources, http://www.ncbi.nlm.nih.gov/genome/guide/human/
    1. Marshfield Medical Research Foundation, http://research.marshfieldclinic.org/genetics/
    1. Mega2 version 2.5 (2001), http://watson.hgen.pitt.edu/mega2.html
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim

References

    1. Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ (2001) MRI measurement of brain iron in patients with restless legs syndrome. Neurology 56:263–265 - PubMed
    1. Allen RP, Earley CJ (2001) Restless legs syndrome: a review of clinical and pathophysiologic features. J Clin Neurophysiol 18:128–14710.1097/00004691-200103000-00004 - DOI - PubMed
    1. Allen RP, La Buda MC, Becker P, Earley CJ (2002) Family history study of the restless legs syndrome. Sleep Med Suppl 3:S3–S7 - PubMed
    1. Allen RP, Kushida CA, Atkinson MJ (2003a) Factor analysis of the International Restless Legs Syndrome Study Group’s scale for restless legs severity. Sleep Med 4:133–13510.1016/S1389-9457(02)00193-4 - DOI - PubMed
    1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J (2003b) Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 4:101–11910.1016/S1389-9457(03)00010-8 - DOI - PubMed

Publication types

Substances

Associated data