GAMETIC BUT NOT SOMATIC INSTABILITY OF CAG REPEAT LENGTH IN HUNTINGTONS-DISEASE

被引：159

作者：

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

机构：

[1] BOSTON UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02118 USA

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

[3] MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA

[4] UNIV ROCHESTER, MED CTR, DEPT NEUROL, ROCHESTER, NY 14642 USA

[5] MCLEAN HOSP, BRAIN TISSUE RESOURCE CTR, BELMONT, MA 02178 USA

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

[7] BAYLOR UNIV, COLL MED, HOUSTON, TX 77009 USA

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

[9] UNIV MIAMI, DEPT NEUROL, MIAMI, FL 33136 USA

[10] UNIV MISSISSIPPI, MED CTR, JACKSON, MS 39216 USA

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

[12] MASSACHUSETTS GEN HOSP, CTR NEUROSCI, MOLEC NEUROPATHOL LAB, BOSTON, MA 02129 USA

[13] UNIV ZULIA, MARACAIBO, VENEZUELA

[14] COLUMBIA UNIV COLL PHYS & SURG, DEPT NEUROL, NEW YORK, NY 10032 USA

[15] COLUMBIA UNIV COLL PHYS & SURG, DEPT PSYCHIAT, NEW YORK, NY 10032 USA

[16] HEREDITARY DIS FDN, SANTA MONICA, CA 90401 USA

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

来源：

JOURNAL OF MEDICAL GENETICS | 1993年 / 30卷 / 12期

关键词：

D O I：

10.1136/jmg.30.12.982

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Instability of a CAG repeat in 4p16.3 has been found in Huntington's disease (HD) chromosomes. Unlike a similar repeat in the fragile X syndrome, the expanded HD repeat showed no evidence of somatic instability in a comparison of blood, lymphoblast, and brain DNA from the same persons. Four pairs of monozygotic HD twins displayed identical CAG repeat lengths suggesting that repeat size is determined in gametogenesis. In contrast with the fragile X syndrome and with HD somatic tissue, mosaicism was readily detected as a diffuse spread of repeat lengths in DNA from HD sperm samples. Typically, the modal repeat size was larger in the sperm DNA than in corresponding lymphoblast DNA, with the greatest degree of gametic mosaicism coinciding with the longest somatic CAG repeats. These data indicate that the developmental timing of repeat instability appears to differ between HD and fragile X syndrome, and that the fundamental mechanisms leading to repeat expansion may therefore be distinct.

引用

页码：982 / 986

页数：5

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