PMID- 18252220
OWN - NLM
STAT- MEDLINE
DCOM- 20080317
LR  - 20220331
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 82
IP  - 2
DP  - 2008 Feb
TI  - Mechanisms and consequences of small supernumerary marker chromosomes: from 
      Barbara McClintock to modern genetic-counseling issues.
PG  - 398-410
LID - 10.1016/j.ajhg.2007.10.013 [doi]
AB  - Supernumerary marker chromosomes (SMCs) are common, but their molecular content 
      and mechanism of origin are often not precisely characterized. We analyzed all 
      centromere regions to identify the junction between the unique chromosome arm and 
      the pericentromeric repeats. A molecular-ruler clone panel for each chromosome 
      arm was developed and used for the design of a custom oligonucleotide array. Of 
      27 nonsatellited SMCs analyzed by array comparative genomic hybridization (aCGH) 
      and/or fluorescence in situ hybridization (FISH), seven (approximately 26%) were 
      shown to be unique sequence negative. Of the 20 unique-sequence-positive SMCs, 
      the average unique DNA content was approximately 6.5 Mb (range 0.3-22.2 Mb) and 
      33 known genes (range 0-149). Of the 14 informative nonacrocentric SMCs, five 
      (approximately 36%) contained unique DNA from both the p and q arms, whereas nine 
      (approximately 64%) contained unique DNA from only one arm. The latter cases are 
      consistent with ring-chromosome formation by centromere misdivision, as first 
      described by McClintock in maize. In one case, a r(4) containing approximately 
      4.4 Mb of unique DNA from 4p was also present in the proband's mother. However, 
      FISH revealed a cryptic deletion in one chromosome 4 and reduced alpha satellite 
      in the del(4) and r(4), indicating that the mother was a balanced ring and 
      deletion carrier. Our data, and recent reports in the literature, suggest that 
      this "McClintock mechanism" of small-ring formation might be the predominant 
      mechanism of origin. Comprehensive analysis of SMCs by aCGH and FISH can 
      distinguish unique-negative from unique-positive cases, determine the precise 
      gene content, and provide information on mechanism of origin, inheritance, and 
      recurrence risk.
FAU - Baldwin, Erin L
AU  - Baldwin EL
AD  - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 
      30322, USA.
FAU - May, Lorraine F
AU  - May LF
FAU - Justice, April N
AU  - Justice AN
FAU - Martin, Christa L
AU  - Martin CL
FAU - Ledbetter, David H
AU  - Ledbetter DH
LA  - eng
GR  - R01 MH074090/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Centromere/genetics
MH  - *Chromosome Aberrations
MH  - Chromosomes, Artificial, Bacterial/genetics
MH  - Genetic Markers/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Nucleic Acid Hybridization
MH  - *Ring Chromosomes
PMC - PMC2427313
EDAT- 2008/02/07 09:00
MHDA- 2008/03/18 09:00
PMCR- 2008/08/08
CRDT- 2008/02/07 09:00
PHST- 2007/08/07 00:00 [received]
PHST- 2007/10/05 00:00 [revised]
PHST- 2007/10/18 00:00 [accepted]
PHST- 2008/02/07 09:00 [pubmed]
PHST- 2008/03/18 09:00 [medline]
PHST- 2008/02/07 09:00 [entrez]
PHST- 2008/08/08 00:00 [pmc-release]
AID - S0002-9297(08)00092-X [pii]
AID - AJHG59 [pii]
AID - 10.1016/j.ajhg.2007.10.013 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2008 Feb;82(2):398-410. doi: 10.1016/j.ajhg.2007.10.013.