TY - JOUR
T1 - Identification of novel imprinted transcripts in the Prader-Willi syndrome and Angelman syndrome deletion region
T2 - Further evidence for regional imprinting control
AU - Lee, Syann
AU - Wevrick, Rachel
N1 - Funding Information:
We thank Jocelyn Carroll for excellent technical assistance, Heather MacDonald for contributions to the early stages of this study, and members of the Wevrick laboratory for helpful discussions. Samples used in this study were provided by the University of Miami Brain and Tissue Bank for Developmental Disorders, Dr. Arthur Beaudet, and Dr. Marc Lalande. This work was supported by an operating grant from the Medical Research Council of Canada and a Basil O'Connor Scholarship from the March of Dimes. R.W. is a scholar of the Alberta Heritage Foundation for Medical Research and the Medical Research Council of Canada. S.L. holds a studentship from the Alberta Heritage Foundation for Medical Research.
PY - 2000
Y1 - 2000
N2 - Deletions and other abnormalities of human chromosome 15q11-q13 are associated with two developmental disorders, Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Loss of expression of imprinted, paternally expressed genes has been implicated in PWS. However, the number of imprinted genes that contribute to PWS, and the range over which the imprinting signal acts to silence one copy of the gene in a parent-of-origin-specific manner, are unknown. To identify additional imprinted genes that could contribute to the PWS phenotype and to understand the regional control of imprinting in 15q11- q13, we have constructed an imprinted transcript map of the PWS-AS deletion interval. The imprinting status of 22 expressed sequence tags derived from the radiation-hybrid human transcript maps or physical maps was determined in a reverse transcriptase-PCR assay and correlated with the position of the transcripts on the physical map. Seven new paternally expressed transcripts localize to an ~1.5-Mb domain surrounding the SNRPN-associated imprinting center, which already includes four imprinted, paternally expressed genes. All other tested new transcripts in the deletion region were expressed from both alleles. A domain of exclusive paternal expression surrounding the imprinting center suggests strong regional control of the imprinting process. This study provides the means for further investigation of additional genes that cause or modify the phenotypes associated with rearrangements of 15q11- q13.
AB - Deletions and other abnormalities of human chromosome 15q11-q13 are associated with two developmental disorders, Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Loss of expression of imprinted, paternally expressed genes has been implicated in PWS. However, the number of imprinted genes that contribute to PWS, and the range over which the imprinting signal acts to silence one copy of the gene in a parent-of-origin-specific manner, are unknown. To identify additional imprinted genes that could contribute to the PWS phenotype and to understand the regional control of imprinting in 15q11- q13, we have constructed an imprinted transcript map of the PWS-AS deletion interval. The imprinting status of 22 expressed sequence tags derived from the radiation-hybrid human transcript maps or physical maps was determined in a reverse transcriptase-PCR assay and correlated with the position of the transcripts on the physical map. Seven new paternally expressed transcripts localize to an ~1.5-Mb domain surrounding the SNRPN-associated imprinting center, which already includes four imprinted, paternally expressed genes. All other tested new transcripts in the deletion region were expressed from both alleles. A domain of exclusive paternal expression surrounding the imprinting center suggests strong regional control of the imprinting process. This study provides the means for further investigation of additional genes that cause or modify the phenotypes associated with rearrangements of 15q11- q13.
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U2 - 10.1086/302817
DO - 10.1086/302817
M3 - Article
C2 - 10712201
AN - SCOPUS:0033942565
SN - 0002-9297
VL - 66
SP - 848
EP - 858
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -