Elucidating the mechanisms of paternal non-disjunction of chromosome 21 in humans

被引:71
作者
Savage, AR
Petersen, MB
Pettay, D
Taft, L
Allran, K
Freeman, SB
Karadima, G
Avramopoulos, D
Torfs, C
Mikkelsen, M
Hassold, TJ
Sherman, SL [1 ]
机构
[1] Emory Univ, Sch Med, Dept Genet, Atlanta, GA 30322 USA
[2] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Sch Med, Ctr Human Genet, Cleveland, OH USA
[4] Inst Child Hlth, Dept Genet, Athens, Greece
[5] JF Kennedy Inst, Danish Ctr Human Genome Res, Glostrup, Denmark
[6] Calif Birth Defects Monitoring Program, Emeryville, CA USA
关键词
D O I
10.1093/hmg/7.8.1221
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Paternal non-disjunction of chromosome 21 accounts for 5-10% of Down syndrome cases, therefore, relative to the maternally derived cases, little is known about paternally derived trisomy 21, We present the first analysis of recombination and non-disjunction for a large paternally derived population of free trisomy 21 conceptuses (n = 67). Unlike maternal cases where the ratio of meiosis I(MI) to meiosis II(MII) errors is 3:1, a near 1:1 ratio exists among paternal cases, with a slight excess of MII errors. We found no paternal age effect for the overall population nor when classifying cases according to stage of non-disjunction error. Among 22 MI cases, only five had an observable recombinant event. This differs significantly from the 11 expected events (P < 0.02, Fisher's exact), suggesting reduced recombination along the non-disjoined chromosomes 21 involved in paternal MI nondisjunction. No difference in recombination was detected among 27 paternal MII cases as compared with controls. However, cases exhibited a slight increase in the frequency of proximal and medial exchange when compared with controls (0.37 versus 0.28, respectively). Lastly, this study confirmed previous reports of excess male probands among paternally derived trisomy 21 cases. However, we report evidence suggesting an MII stage-specific sex ratio disturbance where 2.5 male probands were found for each female proband, Classification of MII cases based on the position of the exchange event suggested that the proband sex ratio disturbance was restricted to non-telomeric exchange cases. Based on these findings, we propose new models to explain the association between paternally derived trisomy 21 and excessive male probands.
引用
收藏
页码:1221 / 1227
页数:7
相关论文
共 31 条
[1]   First-meiotic-division nondisjunction in human oocytes [J].
Angell, R .
AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (01) :23-32
[2]   MITOTIC ERRORS IN SOMATIC-CELLS CAUSE TRISOMY-21 IN ABOUT 4.5-PERCENT OF CASES AND ARE NOT ASSOCIATED WITH ADVANCED MATERNAL AGE [J].
ANTONARAKIS, SE ;
AVRAMOPOULOS, D ;
BLOUIN, JL ;
TALBOT, CC ;
SCHINZEL, AA .
NATURE GENETICS, 1993, 3 (02) :146-150
[3]   PARENTAL ORIGIN OF THE EXTRA CHROMOSOME IN TRISOMY-21 AS INDICATED BY ANALYSIS OF DNA POLYMORPHISMS [J].
ANTONARAKIS, SE .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (13) :872-876
[4]  
BERNHEIM A, 1979, ANN GENET-PARIS, V22, P112
[5]   Tam1, a telomere-associated meiotic protein, functions in chromosome synapsis and crossover interference [J].
Chua, PR ;
Roeder, GS .
GENES & DEVELOPMENT, 1997, 11 (14) :1786-1800
[6]  
Fryns J P, 1987, Birth Defects Orig Artic Ser, V23, P7
[7]  
Griffin DK, 1996, AM J HUM GENET, V59, P1108
[8]  
HASSOLD T, 1985, AM J HUM GENET, V37, P965
[9]   SEX-RATIO IN SPONTANEOUS-ABORTIONS [J].
HASSOLD, T ;
QUILLEN, SD ;
YAMANE, JA .
ANNALS OF HUMAN GENETICS, 1983, 47 (JAN) :39-47
[10]  
Hassold TJ, 1998, CURR TOP DEV BIOL, V37, P383