GAMETIC AND SOMATIC TISSUE-SPECIFIC HETEROGENEITY OF THE EXPANDED SCA1 CAG REPEAT IN SPINOCEREBELLAR ATAXIA TYPE-1

被引：166

作者：

CHONG, SS

MCCALL, AE

COTA, J

SUBRAMONY, SH

ORR, HT

HUGHES, MR

ZOGHBI, HY

机构：

[1] BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030

[2] BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030

[3] BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030

[4] NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892

[5] UNIV MISSISSIPPI,MED CTR,JACKSON,MS 39216

[6] UNIV MINNESOTA,INST HUMAN GENET,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455

来源：

NATURE GENETICS | 1995年 / 10卷 / 03期

关键词：

D O I：

10.1038/ng0795-344

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Spinocerebellar ataxia type 1 is associated with expansion of an unstable CAG repeat within the SCA1 gene. Male gametic heterogeneity of the expanded repeat is demonstrated using single sperm and low-copy genome analysis. Low-copy genome analysis of peripheral blood also reveals somatic heterogeneity of the expanded SCA1 allele, thus establishing mitotic instability at this locus. Comparative analysis of a large normal allele and a small affected allele suggests a role of midstream CAT interspersions in stabilizing long (CAG)(n) stretches. Within the brain, tissue-specific mosaicism of the expanded allele is also observed. The differences in SCA1 allele heterogeneity between sperm and blood and within the brain parallels the findings in Huntington disease, suggesting that both disorders share a common mechanism for tissue-specific instability.

引用

页码：344 / 350

页数：7

共 40 条

[11] COMPLEX GENE CONVERSION EVENTS IN GERMLINE MUTATION AT HUMAN MINISATELLITES [J].

JEFFREYS, AJ ;

TAMAKI, K ;

MACLEOD, A ;

MONCKTON, DG ;

NEIL, DL ;

ARMOUR, JAL .

NATURE GENETICS, 1994, 6 (02) :136-145

[12]

JODICE C, 1994, AM J HUM GENET, V54, P959

[13] CAG EXPANSIONS IN A NOVEL GENE FOR MACHADO-JOSEPH DISEASE AT CHROMOSOME 14Q32.1 [J].

KAWAGUCHI, Y ;

OKAMOTO, T ;

TANIWAKI, M ;

AIZAWA, M ;

INOUE, M ;

KATAYAMA, S ;

KAWAKAMI, H ;

NAKAMURA, S ;

NISHIMURA, M ;

AKIGUCHI, I ;

KIMURA, J ;

NARUMIYA, S ;

KAKIZUKA, A .

NATURE GENETICS, 1994, 8 (03) :221-228

[14]

KOLDE R, 1994, NAT GENET, V6, P9

[15] CRYPTIC AND POLAR VARIATION OF THE FRAGILE-X REPEAT COULD RESULT IN PREDISPOSING NORMAL ALLELES [J].

KUNST, CB ;

WARREN, ST .

CELL, 1994, 77 (06) :853-861

[16] ANDROGEN RECEPTOR GENE-MUTATIONS IN X-LINKED SPINAL AND BULBAR MUSCULAR-ATROPHY [J].

LASPADA, AR ;

WILSON, EM ;

LUBAHN, DB ;

HARDING, AE ;

FISCHBECK, KH .

NATURE, 1991, 352 (6330) :77-79

[17] GAMETIC BUT NOT SOMATIC INSTABILITY OF CAG REPEAT LENGTH IN HUNTINGTONS-DISEASE [J].

MACDONALD, ME ;

BARNES, G ;

SRINIDHI, J ;

DUYAO, MP ;

AMBROSE, CM ;

MYERS, RH ;

GRAY, J ;

CONNEALLY, PM ;

YOUNG, A ;

PENNEY, J ;

SHOULSON, I ;

HOLLINGSWORTH, Z ;

KOROSHETZ, W ;

BIRD, E ;

VONSATTEL, JP ;

BONILLA, E ;

MOSCOWITZ, C ;

PENCHASZADEH, G ;

BRZUSTOWICZ, L ;

ALVIR, J ;

CONDE, JB ;

CHA, JH ;

DURE, L ;

GOMEZ, F ;

RAMOSARROYO, M ;

SANCHEZRAMOS, J ;

SNODGRASS, SR ;

DEYOUNG, M ;

WEXLER, NS ;

MACFARLANE, H ;

ANDERSON, MA ;

JENKINS, B ;

GUSELLA, JF .

JOURNAL OF MEDICAL GENETICS, 1993, 30 (12) :982-986

[18] PRESYMPTOMATIC ANALYSIS OF SPINOCEREBELLAR ATAXIA TYPE-1 (SCA1) VIA THE EXPANSION OF THE SCA1 CAG-REPEAT IN A LARGE PEDIGREE DISPLAYING ANTICIPATION AND PARENTAL MALE BIAS [J].

MATILLA, T ;

VOLPINI, V ;

GENIS, D ;

ROSELL, J ;

CORRAL, J ;

DAVALOS, A ;

MOLINS, A ;

ESTIVILL, X .

HUMAN MOLECULAR GENETICS, 1993, 2 (12) :2123-2128

[19] DENTATORUBRAL AND PALLIDOLUYSIAN ATROPHY EXPANSION OF AN UNSTABLE CAG TRINUCLEOTIDE ON CHROMOSOME-12P [J].

NAGAFUCHI, S ;

YANAGISAWA, H ;

SATO, K ;

SHIRAYAMA, T ;

OHSAKI, E ;

BUNDO, M ;

TAKEDA, T ;

TADOKORO, K ;

KONDO, I ;

MURAYAMA, N ;

TANAKA, Y ;

KIKUSHIMA, H ;

UMINO, K ;

KUROSAWA, H ;

FURUKAWA, T ;

NIHEI, K ;

INOUE, T ;

SANO, A ;

KOMURE, O ;

TAKAHASHI, M ;

YOSHIZAWA, T ;

KANAZAWA, I ;

YAMADA, M .

NATURE GENETICS, 1994, 6 (01) :14-18

[20] STRUCTURE AND EXPRESSION OF THE GENE RESPONSIBLE FOR THE TRIPLET REPEAT DISORDER, DENTATORUBRAL AND PALLIDOLUYSIAN ATROPHY (DRPLA) [J].