Nucleolar Organizer Region Variants As a Risk Factor for Down Syndrome

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1985 Nov 1

PMID 2934977

Citations 14

Authors

C K Jackson-Cook

D B Flannery

L A Corey

W E Nance

J A Brown

Affiliations

Soon will be listed here.

Abstract

An unusual nucleolar organizer region (NOR) heteromorphism was noted among 13 of 41 parents in whom nondisjunction leading to trisomy 21 was known to have occurred. In contrast, only one of these double NOR (dNOR) variants was found among the 41 normal spouses and none were seen among 50 control individuals. In two dNOR(+) families, a second child with trisomy 21 was conceived. In both families, the extra chromosome in each child was contributed by the parent who carried the dNOR variant and resulted from a recurrent meiosis I error. Our data suggest that the dNOR heteromorphism may play a role in meiotic nondisjunction and could be associated with as much as a 20-fold increased risk for having offspring with trisomy 21.

Citing Articles

Epigenetics in Turner syndrome.

Alvarez-Nava F, Lanes R Clin Epigenetics. 2018; 10:45.

PMID: 29636833 PMC: 5889574. DOI: 10.1186/s13148-018-0477-0.

Recurrent Trisomies: Chance or Inherited Predisposition?.

Ulm J J Genet Couns. 2015; 8(2):109-17.

PMID: 26141972 DOI: 10.1023/A:1022842931704.

Constitutional and acquired autosomal aneuploidy.

Jackson-Cook C Clin Lab Med. 2011; 31(4):481-511, vii.

PMID: 22118733 PMC: 3269043. DOI: 10.1016/j.cll.2011.08.002.

A novel tau transcript in cultured human neuroblastoma cells expressing nuclear tau.

Wang Y, Loomis P, Zinkowski R, Binder L J Cell Biol. 1993; 121(2):257-67.

PMID: 8468346 PMC: 2200092. DOI: 10.1083/jcb.121.2.257.

Analysis of nucleolar organizing regions in parents of trisomic spontaneous abortions.

Hassold T, Jacobs P, Pettay D Hum Genet. 1987; 76(4):381-4.

PMID: 3610159 DOI: 10.1007/BF00272449.

References

Archidiacono N, De Capoa A, Ferraro M, Pelliccia F, Rocchi A, Rocchi M . Nucleolus organizer and N-band distribution in morphologic and fluorescence variants of human chromosomes. Hum Genet. 1977; 37(3):285-9. DOI: 10.1007/BF00393610. View

Hayata I, Oshimura M, Sandberg A . N-band polymorphism of human acrocentric chromosomes and its relevance to satellite association. Hum Genet. 1977; 36(1):55-61. DOI: 10.1007/BF00390436. View

Markovic V, Worton R, Berg J . Evidence for the inheritance of silver-stained nucleolus organizer regions. Hum Genet. 1978; 41(2):181-7. DOI: 10.1007/BF00273100. View

Hansson A, Mikkelsen M . The origin of the extra chromosome 21 in Down syndrome. Studies of fluorescent variants and satelite association in 26 informative families. Cytogenet Cell Genet. 1978; 20(1-6):194-203. DOI: 10.1159/000130851. View

Miller D, BREG W, Warburton D, Dev V, MILLER O . Regulation of rRNA gene expression in a human familial 14p+ marker chromosome. Hum Genet. 1978; 43(3):289-97. DOI: 10.1007/BF00278836. View

Lau Y, Wertelecki W, Pfeiffer R, Arrighi F . Cytological analyses of 14p+ variant by means of N-banding and combinations of silver staining and chromosome bandings. Hum Genet. 1979; 46(1):75-82. DOI: 10.1007/BF00278904. View

Martin A, Miller L, Simpson J, Thomas C, Rzeszotarski M, Elias S . Localization of the nucleolar organizer by computer-aided analysis of a variant no. 21 in a human isolate. Hum Genet. 1979; 48(2):211-9. DOI: 10.1007/BF00286906. View

Balicek P, Zizka J . Intercalar satellites of human acrocentric chromosomes as a cytological manifestation of polymorphism in GC-rich material?. Hum Genet. 1980; 54(3):343-7. DOI: 10.1007/BF00291580. View

Mirre C, Hartung M, Stahl A . Association of ribosomal genes in the fibrillar center of the nucleolus: a factor influencing translocation and nondisjunction in the human meiotic oocyte. Proc Natl Acad Sci U S A. 1980; 77(10):6017-21. PMC: 350204. DOI: 10.1073/pnas.77.10.6017. View

10.

Sofuni T, Tanabe K, Awa A . Chromosome heteromorphisms in the Japanese. II. Nucleolus organizer regions of variant chromosomes in D and G groups. Hum Genet. 1980; 55(2):265-70. DOI: 10.1007/BF00291776. View

11.

Hook E, Cross P . Temporal increase in the rate of Down syndrome livebirths to older mothers in New York State. J Med Genet. 1981; 18(1):29-30. PMC: 1048653. DOI: 10.1136/jmg.18.1.29. View

12.

Bernstein R, Dawson B, Griffiths J . Human inherited marker chromosome 22 short-arm enlargement: investigation of rDNA gene multiplicity, Ag-band size, and acrocentric association. Hum Genet. 1981; 58(2):135-9. DOI: 10.1007/BF00278697. View

13.

Mikkelsen M, POULSEN H, Grinsted J, Lange A . Non-disjunction in trisomy 21: study of chromosomal heteromorphisms in 110 families. Ann Hum Genet. 1980; 44(1):17-28. DOI: 10.1111/j.1469-1809.1980.tb00942.x. View

14.

van Melle G . Is it always the same NOR that is more active in a pair of acrocentrics with distinct AG-stainings?. Hum Genet. 1981; 59(2):185. DOI: 10.1007/BF00293075. View

15.

Werner W, Herrmann F, John B . Cytogenetic studies of a family with trisomy 21 mosaicism in two successive generations as the cause of Down's syndrome. Hum Genet. 1982; 60(2):202-4. DOI: 10.1007/BF00569714. View

16.

Jacobs P, Mayer M . The origin of human trisomy: a study of heteromorphisms and satellite associations. Ann Hum Genet. 1981; 45(4):357-65. DOI: 10.1111/j.1469-1809.1981.tb00349.x. View

17.

ZAKHAROV A, Davudov A, Benjush V, Egolina N . Polymorphisms of Ag-stained nucleolar organizer regions in man. Hum Genet. 1982; 60(4):334-9. DOI: 10.1007/BF00569214. View

18.

Mikkelsen M . Parental origin of the extra chromosome in Down's Syndrome. J Ment Defic Res. 1982; 26(Pt 3):143-51. DOI: 10.1111/j.1365-2788.1982.tb00141.x. View

19.

Morton C, Brown J, Holmes W, Nance W, Wolf B . Stain intensity of human nucleolus organizer region reflects incorporation of uridine into mature ribosomal RNA. Exp Cell Res. 1983; 145(2):405-13. DOI: 10.1016/0014-4827(83)90019-8. View

20.

Schmid M, Muller H, Stasch S, Engel W . Silver staining of nucleolus organizer regions during human spermatogenesis. Hum Genet. 1983; 64(4):363-70. DOI: 10.1007/BF00292368. View