The imprinted gene and parent-of-origin effect database now includes p
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《核酸研究医学期刊》
Department of Biology, Massachusetts College of Liberal Arts North Adams, MA 01247, USA 1Department of Microbiology, University of Otago PO Box 56, Dunedin, New Zealand 2Department of Biochemistry, University of Otago PO Box 56, Dunedin, New Zealand
*To whom correspondence should be addressed. Tel: +1 413 662 5548; Email: rglaser@mcla.edu
ABSTRACT
The imprinted gene and parent-of-origin effect database (www.otago.ac.nz/IGC) consists of two sections. One section catalogues the current literature on imprinted genes in humans and animals. The second, and new, section catalogues current reports of parental origin of de novo mutations in humans alone. The addition of a catalogue of de novo mutations that show a parent-of-origin effect expands the scope of the database and provides a useful tool for examining parental origin trends for different types of spontaneous mutations. This new section includes >1700 mutations, found in 59 different disorders. The 85 imprinted genes are described in 152 entries from several mammalian species. In addition, >300 other entries describe a range of reported parent-of-origin effects in animals.
INTRODUCTION
‘Parent-of-origin effects’ is a broad term that encompasses two distinct phenomena—parent-of-origin effects on transcription, and parent-of-origin effects on mutation rates. A parent-of-origin effect on transcription, or genomic imprinting, results from epigenetic modification of the genome which, in turn, results in unequal transcription of parental alleles. For these imprinted genes, expression of the alleles is dependent upon the sex of the parent from which they were inherited (1). A parent-of-origin effect on mutation rate, however, refers to the preferential occurrence of some spontaneous mutations in either the father's or the mother's germ line. The mechanisms by which these spontaneous mutations arise depend upon the parental germ line in which the mutation occurred. For example, base substitutions, arising from errors during replication, tend to be paternal in origin, owing to the greater number of cell divisions in spermatogenesis as compared with oogenesis (2). Chromosomal abnormalities, however, tend to be maternal in origin. Oocytes are arrested in prophase of meiosis I until sexual maturity, when one oocyte per month is selected to resume the cell cycle. It is thought that the longer the oocytes are arrested in meiosis, the greater the chance for a nondisjunction event to occur (3). Advanced parental age seems to influence the development of some, but not all, of these mutations (also referred to as the paternal or maternal age effect) (2).
THE DATABASE
In 1998, the catalogue of imprinted genes and parent-of-origin effects was first published (4). This catalogue served as the basis for the development of a more comprehensive, searchable, online database, made publicly available in 1999. The original database included 41 imprinted genes, and other parent-of-origin effects, including some records on the parental origin of spontaneous mutations (5).
We have added recently a comprehensive section on spontaneous mutations that show a bias with respect to their parental origin. This new part of the database can be searched according to mutation type, disorder, chromosomal location, gene name and inheritance pattern. Each entry in the database is hyperlinked to the relevant reference in PubMed. Outcomes of the search are presented in a tabular format with the following information: disorder, inheritance pattern, incidence of disorder, gene name, chromosomal location, evidence of a paternal or maternal age effect, mutation type and any recurrent mutations associated with a parent-of-origin effect, number of paternal mutations, number of maternal mutations and PubMed reference (e.g. Table 1). In the case of base substitutions, data are separated according to the type of base substitution (missense mutation, nonsense mutation or splice site mutation), whether the mutation is a transition or transversion mutation, and whether the base substitution falls within a CpG dinucleotide. For deletions and insertions, the distinction is made between large deletions and insertions (>20 bp) and small deletions and insertions (<20 bp). This size distinction is made based upon the possibility of different mechanisms contributing to these different types of mutations, and therefore potentially different parental origins (2). In general, large deletions do not appear to have a parent-of-origin effect, whereas small deletions tend to be more paternal in origin.
Table 1 Example of report for parental origin of de novo mutations showing base substitutions within a CpG dinucleotide
Currently, >1700 mutations with a parent-of-origin effect are catalogued in this database. These mutations are found in 59 different disorders. Large deletions comprise the largest category in this database, with 900 mutations catalogued. Base substitutions form the second largest category in the database, with 400 mutations.
The other major section of the database includes known imprinted genes and observations of other putatively imprinted genes. Of the 464 database entries, 152 entries describe 85 unique imprinted genes in humans, mice, cattle, sheep, pigs, rats and marsupials, as well as 14 genes for which the evidence of imprinting is conflicting or provisional. The imprinted genes have been described recently in a review publication (17). The phenotypic consequences of human and mouse uniparental disomies are described in 31 entries. An additional 186 entries report parent-of-origin effects in the transmission or linkage of simple and complex genetic conditions including human diseases and animal quantitative traits.
DATABASE ACCESS AND USAGE
The imprinted gene and parent-of-origin effect database is housed at the University of Otago in Dunedin, New Zealand and can be accessed at www.otago.ac.nz/IGC. The database is maintained by the corresponding authors who welcome submissions and comments and is updated as new literature is published. Submissions to the imprinted gene database should be directed to I.M.M. and submissions to the parental origin of de novo mutations database should be directed to R.L.G. Users of the database are asked to cite this article in their publication.
ACKNOWLEDGEMENTS
We thank Sue Harvey for management of the database. Support has been provided by the Child Cancer Foundation, the Health Research Council of New Zealand and the National Centre for Research on Growth and Development. Funding to pay the Open Access publication charges for this article was provided by the Health Research Council of New Zealand.
REFERENCES
Reik, W. and Walter, J. (2001) Genomic imprinting: parental influence on the genome Nature Rev. Genet, . 2, 21–32 .
Glaser, R.L. and Jabs, E.W. (2004) Dear Old Dad Sci. Aging Knowledge Environ, . 2004, re1. Review .
Crow, J.F. (2000) The origins, patterns and implications of human spontaneous mutation Nature Rev. Genet, . 1, 40–47 .
Morison, I.M. and Reeve, A.E. (1998) A catalogue of imprinted genes and parent-of-origin effects in humans and animals Hum. Mol. Genet, . 7, 1599–1609 .
Morison, I.M., Paton, C.J., Cleverly, S.D. (2001) The imprinted gene and parent-of-origin effect database Nucleic Acids Res, . 29, 275–276 .
Moloney, D.M., Slaney, S.F., Oldridge, M., et al. (1996) Exclusive paternal origin of new mutations in Apert syndrome Nat. Genet, . 13, 48–53 .
Wilkin, D.J., Szabo, J.K., Cameron, R., et al. (1998) Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome Am. J. Hum. Genet, . 63, 711–716 .
Eriksson, M., Brown, W.T., Gordon, L.B., et al. (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome Nature, 423, 293–298 .
D'Apice, M.R., Tenconi, R., Mammi, I., et al. (2004) Paternal origin of LMNA mutations in Hutchinson-Gilford progeria Clin. Genet, . 65, 52–54 .
Rannan-Eliya, S.V., Taylor, I.B., De Heer, I.M., et al. (2004) Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis Hum. Genet, . 115, 200–207 .
Richards, F.M., Payne, S.J., Zbar, B., et al. (1995) Molecular analysis of de novo germline mutations in the von Hippel-Lindau disease gene Hum. Mol. Genet, . 4, 2139–2143 .
Girard, M., Couvert, P., Carrie, A., et al. (2001) Parental origin of de novo MECP2 mutations in Rett syndrome Eur. J. Hum. Genet, . 9, 231–236 .
Amir, R.E., Van den Veyver, I.B., Schultz, R., et al. (2000) Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes Ann Neurol, . 47, 670–679 .
Trappe, R., Laccone, F., Cobilanschi, J., et al. (2001) MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin Am. J. Hum. Genet, . 68, 1093–1101 .
Ketterling, R.P., Vielhaber, E., Li, X., et al. (1999) Germline origins in the human F9 gene: frequent G:C–>A:T mosaicism and increased mutations with advanced maternal age Hum. Genet, . 105, 629–640 .
Green, P.M., Saad, S., Lewis, C.M., et al. (1999) Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B Am. J. Hum. Genet, . 65, 1572–1579 .
Morison, I.M., Ramsay, J.P., Spencer, H.G. (2005) A census of mammalian imprinting Trends Genet, . 21, 457–465 .(Rivka L. Glaser*, Joshua P. Ramsay1 and )
*To whom correspondence should be addressed. Tel: +1 413 662 5548; Email: rglaser@mcla.edu
ABSTRACT
The imprinted gene and parent-of-origin effect database (www.otago.ac.nz/IGC) consists of two sections. One section catalogues the current literature on imprinted genes in humans and animals. The second, and new, section catalogues current reports of parental origin of de novo mutations in humans alone. The addition of a catalogue of de novo mutations that show a parent-of-origin effect expands the scope of the database and provides a useful tool for examining parental origin trends for different types of spontaneous mutations. This new section includes >1700 mutations, found in 59 different disorders. The 85 imprinted genes are described in 152 entries from several mammalian species. In addition, >300 other entries describe a range of reported parent-of-origin effects in animals.
INTRODUCTION
‘Parent-of-origin effects’ is a broad term that encompasses two distinct phenomena—parent-of-origin effects on transcription, and parent-of-origin effects on mutation rates. A parent-of-origin effect on transcription, or genomic imprinting, results from epigenetic modification of the genome which, in turn, results in unequal transcription of parental alleles. For these imprinted genes, expression of the alleles is dependent upon the sex of the parent from which they were inherited (1). A parent-of-origin effect on mutation rate, however, refers to the preferential occurrence of some spontaneous mutations in either the father's or the mother's germ line. The mechanisms by which these spontaneous mutations arise depend upon the parental germ line in which the mutation occurred. For example, base substitutions, arising from errors during replication, tend to be paternal in origin, owing to the greater number of cell divisions in spermatogenesis as compared with oogenesis (2). Chromosomal abnormalities, however, tend to be maternal in origin. Oocytes are arrested in prophase of meiosis I until sexual maturity, when one oocyte per month is selected to resume the cell cycle. It is thought that the longer the oocytes are arrested in meiosis, the greater the chance for a nondisjunction event to occur (3). Advanced parental age seems to influence the development of some, but not all, of these mutations (also referred to as the paternal or maternal age effect) (2).
THE DATABASE
In 1998, the catalogue of imprinted genes and parent-of-origin effects was first published (4). This catalogue served as the basis for the development of a more comprehensive, searchable, online database, made publicly available in 1999. The original database included 41 imprinted genes, and other parent-of-origin effects, including some records on the parental origin of spontaneous mutations (5).
We have added recently a comprehensive section on spontaneous mutations that show a bias with respect to their parental origin. This new part of the database can be searched according to mutation type, disorder, chromosomal location, gene name and inheritance pattern. Each entry in the database is hyperlinked to the relevant reference in PubMed. Outcomes of the search are presented in a tabular format with the following information: disorder, inheritance pattern, incidence of disorder, gene name, chromosomal location, evidence of a paternal or maternal age effect, mutation type and any recurrent mutations associated with a parent-of-origin effect, number of paternal mutations, number of maternal mutations and PubMed reference (e.g. Table 1). In the case of base substitutions, data are separated according to the type of base substitution (missense mutation, nonsense mutation or splice site mutation), whether the mutation is a transition or transversion mutation, and whether the base substitution falls within a CpG dinucleotide. For deletions and insertions, the distinction is made between large deletions and insertions (>20 bp) and small deletions and insertions (<20 bp). This size distinction is made based upon the possibility of different mechanisms contributing to these different types of mutations, and therefore potentially different parental origins (2). In general, large deletions do not appear to have a parent-of-origin effect, whereas small deletions tend to be more paternal in origin.
Table 1 Example of report for parental origin of de novo mutations showing base substitutions within a CpG dinucleotide
Currently, >1700 mutations with a parent-of-origin effect are catalogued in this database. These mutations are found in 59 different disorders. Large deletions comprise the largest category in this database, with 900 mutations catalogued. Base substitutions form the second largest category in the database, with 400 mutations.
The other major section of the database includes known imprinted genes and observations of other putatively imprinted genes. Of the 464 database entries, 152 entries describe 85 unique imprinted genes in humans, mice, cattle, sheep, pigs, rats and marsupials, as well as 14 genes for which the evidence of imprinting is conflicting or provisional. The imprinted genes have been described recently in a review publication (17). The phenotypic consequences of human and mouse uniparental disomies are described in 31 entries. An additional 186 entries report parent-of-origin effects in the transmission or linkage of simple and complex genetic conditions including human diseases and animal quantitative traits.
DATABASE ACCESS AND USAGE
The imprinted gene and parent-of-origin effect database is housed at the University of Otago in Dunedin, New Zealand and can be accessed at www.otago.ac.nz/IGC. The database is maintained by the corresponding authors who welcome submissions and comments and is updated as new literature is published. Submissions to the imprinted gene database should be directed to I.M.M. and submissions to the parental origin of de novo mutations database should be directed to R.L.G. Users of the database are asked to cite this article in their publication.
ACKNOWLEDGEMENTS
We thank Sue Harvey for management of the database. Support has been provided by the Child Cancer Foundation, the Health Research Council of New Zealand and the National Centre for Research on Growth and Development. Funding to pay the Open Access publication charges for this article was provided by the Health Research Council of New Zealand.
REFERENCES
Reik, W. and Walter, J. (2001) Genomic imprinting: parental influence on the genome Nature Rev. Genet, . 2, 21–32 .
Glaser, R.L. and Jabs, E.W. (2004) Dear Old Dad Sci. Aging Knowledge Environ, . 2004, re1. Review .
Crow, J.F. (2000) The origins, patterns and implications of human spontaneous mutation Nature Rev. Genet, . 1, 40–47 .
Morison, I.M. and Reeve, A.E. (1998) A catalogue of imprinted genes and parent-of-origin effects in humans and animals Hum. Mol. Genet, . 7, 1599–1609 .
Morison, I.M., Paton, C.J., Cleverly, S.D. (2001) The imprinted gene and parent-of-origin effect database Nucleic Acids Res, . 29, 275–276 .
Moloney, D.M., Slaney, S.F., Oldridge, M., et al. (1996) Exclusive paternal origin of new mutations in Apert syndrome Nat. Genet, . 13, 48–53 .
Wilkin, D.J., Szabo, J.K., Cameron, R., et al. (1998) Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome Am. J. Hum. Genet, . 63, 711–716 .
Eriksson, M., Brown, W.T., Gordon, L.B., et al. (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome Nature, 423, 293–298 .
D'Apice, M.R., Tenconi, R., Mammi, I., et al. (2004) Paternal origin of LMNA mutations in Hutchinson-Gilford progeria Clin. Genet, . 65, 52–54 .
Rannan-Eliya, S.V., Taylor, I.B., De Heer, I.M., et al. (2004) Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis Hum. Genet, . 115, 200–207 .
Richards, F.M., Payne, S.J., Zbar, B., et al. (1995) Molecular analysis of de novo germline mutations in the von Hippel-Lindau disease gene Hum. Mol. Genet, . 4, 2139–2143 .
Girard, M., Couvert, P., Carrie, A., et al. (2001) Parental origin of de novo MECP2 mutations in Rett syndrome Eur. J. Hum. Genet, . 9, 231–236 .
Amir, R.E., Van den Veyver, I.B., Schultz, R., et al. (2000) Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes Ann Neurol, . 47, 670–679 .
Trappe, R., Laccone, F., Cobilanschi, J., et al. (2001) MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin Am. J. Hum. Genet, . 68, 1093–1101 .
Ketterling, R.P., Vielhaber, E., Li, X., et al. (1999) Germline origins in the human F9 gene: frequent G:C–>A:T mosaicism and increased mutations with advanced maternal age Hum. Genet, . 105, 629–640 .
Green, P.M., Saad, S., Lewis, C.M., et al. (1999) Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B Am. J. Hum. Genet, . 65, 1572–1579 .
Morison, I.M., Ramsay, J.P., Spencer, H.G. (2005) A census of mammalian imprinting Trends Genet, . 21, 457–465 .(Rivka L. Glaser*, Joshua P. Ramsay1 and )