TRINUCLEOTIDE REPEAT LENGTH INSTABILITY AND AGE-OF-ONSET IN HUNTINGTONS-DISEASE

被引：882

作者：

DUYAO, M

AMBROSE, C

MYERS, R

NOVELLETTO, A

PERSICHETTI, F

FRONTALI, M

FOLSTEIN, S

ROSS, C

FRANZ, M

ABBOTT, M

GRAY, J

CONNEALLY, P

YOUNG, A

PENNEY, J

HOLLINGSWORTH, Z

SHOULSON, I

LAZZARINI, A

FALEK, A

KOROSHETZ, W

SAX, D

BIRD, E

VONSATTEL, J

BONILLA, E

ALVIR, J

CONDE, JB

CHA, JH

DURE, L

GOMEZ, F

RAMOS, M

SANCHEZRAMOS, J

SNODGRASS, S

DEYOUNG, M

WEXLER, N

MOSCOWITZ, C

PENCHASZADEH, G

MACFARLANE, H

ANDERSON, M

JENKINS, B

SRINIDHI, J

BARNES, G

GUSELLA, J

MACDONALD, M

机构：

[1] MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129

[2] BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118

[3] UNIV ROMA TOR VERGATA,DEPT BIOL,ROME,ITALY

[4] CNR,INST MED SPERIMENTALE,ROME,ITALY

[5] JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205

[6] INDIANA UNIV,MED CTR,DEPT MED GENET,INDIANAPOLIS,IN 46202

[7] MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114

[8] UNIV ROCHESTER,MED CTR,DEPT NEUROL,ROCHESTER,NY 14642

[9] UNIV MED & DENT NEW JERSEY,DEPT NEUROL,NEW BRUNSWICK,NJ 08903

[10] EMORY UNIV,SCH MED,DEPT PSYCHIAT,ATLANTA,GA 30306

[11] HARVARD UNIV,MCLEAN HOSP,CTR BRAIN TISSUE RESOURCE,BELMONT,MA 02178

[12] HARVARD UNIV,SCH MED,DEPT NEUROPATHOL,BELMONT,MA 02178

[13] UNIV ZULIA,MARACAIBO,VENEZUELA

[14] LONG ISL JEWISH MED CTR,GLEN OAKS,NY 11004

[15] BAYOR UNIV,COLL MED,HOUSTON,TX 77009

[16] KENNEDY KREIGER INST,NEUROSCI LAB,BALTIMORE,MD 21205

[17] HOSP VIRGEN CAMINO,SERV GENET,E-31008 PAMPLONA,SPAIN

[18] UNIV MIAMI,DEPT NEUROL,MIAMI,FL 33136

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

[20] COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROL & PSYCHIAT,NEW YORK,NY 10032

[21] HEREDITARY DIS FDN,SANTA MONICA,CA 90401

[22] HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114

来源：

NATURE GENETICS | 1993年 / 4卷 / 04期

关键词：

D O I：

10.1038/ng0893-387

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

引用

页码：387 / 392

页数：6

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