A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia.
OBJECTIVE
To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD).


METHODS
The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis.


RESULTS
A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb.


CONCLUSIONS
A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD.
Morita
M
M
Day Neuromuscular Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Al-Chalabi
A
A
Andersen
P M
PM
Hosler
B
B
Sapp
P
P
Englund
E
E
Mitchell
J E
JE
Habgood
J J
JJ
de Belleroche
J
J
Xi
J
J
Jongjaroenprasert
W
W
Horvitz
H R
HR
Gunnarsson
L-G
LG
Brown
R H
RH
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003704:Dementia / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D040641:Quantitative Trait Loci / Q000235:genetics*
D005819:Genetic Markers