Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis

被引:406
作者
Shaikh, TH
Kurahashi, H
Saitta, SC
O'Hare, AM
Hu, P
Roe, BA
Driscoll, DA
McDonald-McGinn, DM
Zackai, EH
Budarf, ML
Emanuel, BS
机构
[1] Childrens Hosp Philadelphia, Abramson Res Ctr 1002, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA
[4] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA
关键词
D O I
10.1093/hmg/9.4.489
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
The 22q11.2 deletion syndrome, which includes DiGeorge and velocardiofacial syndromes (DGS/VCFS), is the most common microdeletion syndrome. The majority of deleted patients share a common 3 Nib hemizygous deletion of 22q11.2. The remaining patients include those who have smaller deletions that are nested within the 3 Mb typically deleted region (TDR) and a few with rare deletions that have no overlap with the TDR. The identification of chromosome 22-specific duplicated sequences or low copy repeats (LCRs) near the end-points of the 3 Mb TDR has led to the hypothesis that they mediate deletions of 22q11.2. The entire 3 Mb TDR has been sequenced, permitting detailed investigation of the LCRs and their involvement in the 22q11.2 deletions. Sequence analysis has identified four LCRs within the 3 Mb TDR. Although the LCRs differ in content and organization of shared modules, those modules that are common between them share 97-98% sequence identity with one another. By fluorescence in situ hybridization (FISH) analysis, the end-points of four variant 22q11.2 deletions appear to localize to the LCRs, Pulsed-field gel electrophoresis and Southern hybridization have been used to identify rearranged junction fragments from three variant deletions. Analysis of junction fragments by PCR and sequencing of the PCR products implicate the LCRs directly in the formation of 22q11.2 deletions. The evolutionary origin of the duplications on chromosome 22 has been assessed by FISH analysis of non-human primates. Multiple signals in Old World monkeys suggest that the duplication events may have occurred at least 20-25 million years ago.
引用
收藏
页码:489 / 501
页数:13
相关论文
共 86 条
  • [11] Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients
    Carlson, C
    Sirotkin, H
    Pandita, R
    Goldberg, R
    McKie, J
    Wadey, R
    Patanjali, SR
    Weissman, SM
    AnyaneYeboa, K
    Warburton, D
    Scambler, P
    Shprintzen, R
    Kucherlapati, R
    Morrow, BE
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (03) : 620 - 629
  • [12] E2F-6:: a novel member of the E2F family is an inhibitor of E2F-dependent transcription
    Cartwright, P
    Müller, H
    Wagener, C
    Holm, K
    Helin, K
    [J]. ONCOGENE, 1998, 17 (05) : 611 - 623
  • [13] TRANSIENT SIMULATION OF FREQUENCY-DEPENDENT NONUNIFORM COUPLED LOSSY TRANSMISSION-LINES
    CHANG, FY
    [J]. IEEE TRANSACTIONS ON COMPONENTS PACKAGING AND MANUFACTURING TECHNOLOGY PART B-ADVANCED PACKAGING, 1994, 17 (01): : 3 - 14
  • [14] Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome
    Chen, KS
    Manian, P
    Koeuth, T
    Potocki, L
    Zhao, Q
    Chinault, AC
    Lee, CC
    Lupski, JR
    [J]. NATURE GENETICS, 1997, 17 (02) : 154 - 163
  • [15] SEQUENCE AND ANALYSIS OF THE HUMAN ABL GENE, THE BCR GENE, AND REGIONS INVOLVED IN THE PHILADELPHIA CHROMOSOMAL TRANSLOCATION
    CHISSOE, SL
    BODENTEICH, A
    WANG, YF
    WANG, YP
    BURIAN, D
    CLIFTON, SW
    CRABTREE, J
    FREEMAN, A
    IYER, K
    LI, JA
    MA, YC
    MCLAURY, HJ
    PAN, HQ
    SARHAN, OH
    TOTH, S
    WANG, ZL
    ZHANG, GZ
    HEISTERKAMP, N
    GROFFEN, J
    ROE, BA
    [J]. GENOMICS, 1995, 27 (01) : 67 - 82
  • [16] Large genomic duplicons map to sites of instability in the Prader-Willi/Angelman syndrome chromosome region (15q11-q13)
    Christian, SL
    Fantes, JA
    Mewborn, SK
    Huang, B
    Ledbetter, DH
    [J]. HUMAN MOLECULAR GENETICS, 1999, 8 (06) : 1025 - 1037
  • [17] The organization of the gamma-glutamyl transferase genes and other low copy repeats in human chromosome 22q11
    Collins, JE
    Mungall, AJ
    Badcock, KL
    Fay, JM
    Dunham, I
    [J]. GENOME RESEARCH, 1997, 7 (05) : 522 - 531
  • [18] A DELETION IN CHROMOSOME-22 CAN CAUSE DIGEORGE SYNDROME
    DELACHAPELLE, A
    HERVA, R
    KOIVISTO, M
    AULA, P
    [J]. HUMAN GENETICS, 1981, 57 (03) : 253 - 256
  • [19] Isolation of a novel gene from the DiGeorge syndrome critical region with homology to Drosophila gdl and to human LAMC1 genes
    Demczuk, S
    Thomas, G
    Aurias, A
    [J]. HUMAN MOLECULAR GENETICS, 1996, 5 (05) : 633 - 638
  • [20] DELETIONS AND MICRODELETIONS OF 22Q11.2 IN VELO-CARDIO-FACIAL SYNDROME
    DRISCOLL, DA
    SPINNER, NB
    BUDARF, ML
    MCDONALDMCGINN, DM
    ZACKAI, EH
    GOLDBERG, RB
    SHPRINTZEN, RJ
    SAAL, HM
    ZONANA, J
    JONES, MC
    MASCARELLO, JT
    EMANUEL, BS
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS, 1992, 44 (02): : 261 - 268