TY - JOUR
T1 - HKCa3/KCNN3 potassium channel gene
T2 - Association of longer CAG repeats with schizophrenia in Israeli Ashkenazi Jews, expression in human tissues and localization to chromosome 1q21
AU - Dror, V.
AU - Shamir, E.
AU - Ghanshani, S.
AU - Kimhi, R.
AU - Swartz, M.
AU - Barak, Y.
AU - Weizman, R.
AU - Avivi, L.
AU - Litmanovitch, T.
AU - Fantino, E.
AU - Kalman, K.
AU - Jones, E. G.
AU - Chandy, K. G.
AU - Gargus, J. J.
AU - Gutman, G. A.
AU - Navon, R.
N1 - Funding Information:
This research was supported in part by grant MH59222 to KGC and JJG. We wish to thank D Backlash for his assistance in collecting data from clinical files.
PY - 1999
Y1 - 1999
N2 - We demonstrate a significant association between longer CAG repeats in the hKCa3/KCNN3 calcium-activated potassium channel gene and schizophrenia in Israeli Ashkenazi Jews. We genotyped alleles from 84 Israeli Jewish patients with schizophrenia and from 102 matched controls. The overall allele frequency distribution is significantly different in patients vs controls (P = 0.00017, Wilcoxon Rank Sum test), with patients showing greater lengths of the CAG repeat. Northern blots reveal substantial levels of ~ 9 kb and ~ 13 kb hKCa3/KCNN3 transcripts in brain, striated muscle, spleen and lymph nodes. Within the brain, hKCa3/KCNN3 transcripts are most abundantly expressed in the substantia nigra, lesser amounts are detected in the basal ganglia, amygdala, hippocampus and subthalamic nuclei, while little is seen in the cerebral cortex, cerebellum and thalamus. In situ hybridization reveals abundant hKCa3/KCNN3 message localized within the substantia nigra and ventral tegmental area, and along the distributions of dopaminergic neurons from these regions into the nigrostriatal and mesolimbic pathways. FISH analysis shows that hKCa3/KCNN3 is located on chromosome 1q21.
AB - We demonstrate a significant association between longer CAG repeats in the hKCa3/KCNN3 calcium-activated potassium channel gene and schizophrenia in Israeli Ashkenazi Jews. We genotyped alleles from 84 Israeli Jewish patients with schizophrenia and from 102 matched controls. The overall allele frequency distribution is significantly different in patients vs controls (P = 0.00017, Wilcoxon Rank Sum test), with patients showing greater lengths of the CAG repeat. Northern blots reveal substantial levels of ~ 9 kb and ~ 13 kb hKCa3/KCNN3 transcripts in brain, striated muscle, spleen and lymph nodes. Within the brain, hKCa3/KCNN3 transcripts are most abundantly expressed in the substantia nigra, lesser amounts are detected in the basal ganglia, amygdala, hippocampus and subthalamic nuclei, while little is seen in the cerebral cortex, cerebellum and thalamus. In situ hybridization reveals abundant hKCa3/KCNN3 message localized within the substantia nigra and ventral tegmental area, and along the distributions of dopaminergic neurons from these regions into the nigrostriatal and mesolimbic pathways. FISH analysis shows that hKCa3/KCNN3 is located on chromosome 1q21.
KW - Association study
KW - CAG repeats
KW - Calcium-activated potassium channel
KW - Dopaminergic neurons
KW - FISH
KW - In situ hybridization
KW - SH3 association domain
KW - Schizophrenia
KW - Trinucleotide repeats
KW - hKCa3/KCNN3
UR - http://www.scopus.com/inward/record.url?scp=0013564262&partnerID=8YFLogxK
U2 - 10.1038/sj.mp.4000508
DO - 10.1038/sj.mp.4000508
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C2 - 10395215
AN - SCOPUS:0013564262
SN - 1359-4184
VL - 4
SP - 254
EP - 260
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 3
ER -