Nucleic Acids Research 2005 33(Database Issue):D174-D177; doi:10.1093/nar/gki102
Nucleic Acids Research, 2005, Vol. 33, Database issue D174-D177
© 2005, the authors
Nucleic Acids Research, Vol. 33, Database issue © Oxford University Press 2005; all rights reserved
TPMD: a database and resources of microsatellite marker genotyped in Taiwanese populations
Ya-Hui Chang1,
Wen-Hui Su1,2,
Tso-Ching Lee3,
Hsiao-Fang Sunny Sun4,
Chia-Hsiang Chen5,
Wen-Harn Pan6,
Shih-Feng Tsai1 and
Yuh-Shan Jou1,2,*
1 Division of Molecular and Genomic Medicine, National Health Research Institutes, Taipei 115, Taiwan, 2 Graduate Institute of Life Sciences, National Defense Medical Center, National Defense University, Taipei 114, Taiwan, 3 Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan, 4 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan 701, Taiwan, 5 Department of Psychiatry and Institute of Human Genetics, Tzu-Chi University, Hualien 970, Taiwan and 6 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
* To whom correspondence should be addressed. Tel: +886 2 26524123; Fax: +886 2 27890484; Email: jou{at}nhri.org.tw
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
Received August 13, 2004; Revised and Accepted October 14, 2004
 |
ABSTRACT
|
|---|
Taiwan Polymorphic Marker Database (TPMD) (
http://tpmd.nhri.org.tw/)
is a marker database designed to provide experimental details
and useful marker information allelotyped in Taiwanese populations
accompanied by resources and technical supports. The current
version deposited more than 372 000 allelotyping data from 1425
frequently used and fluorescent-labeled microsatellite markers
with variation types of dinucleotide, trinucleotide and tetranucleotide.
TPMD contains text and map displays with searchable and retrievable
options for marker names, chromosomal location in various human
genome maps and marker heterozygosity in populations of Taiwanese,
Japanese and Caucasian. The integration of marker information
in map display is useful for the selection of high heterozygosity
and commonly used microsatellite markers to refine mapping of
diseases locus followed by identification of disease gene by
positional candidate cloning. In addition, our results indicated
that the number of markers with heterozygosity over 0.7 in Asian
populations is lower than that in Caucasian. To increase accuracy
and facilitate genetic studies using microsatellite markers,
we also list markers with genotyping difficulty due to ambiguity
of allele calling and recommend an optimal set of microsatellite
markers for genotyping in Taiwanese, and possible extension
of genotyping in other Mongoloid populations.
|
INTRODUCTION
|
|---|
Microsatellites, the short (1–13 bp) tandem nucleotide
repeats, are found to comprise
3% but ubiquitously throughout
the human genome (
1). The average density of microsatellites
in human genome is approximately one microsatellite per 2 kb.
However, only a small fraction of microsatellites with properties
such as high heterozygosity, known position along the genetic
map, strong and specific fragment after PCR and easy scoring
of allele sizes are suitable for developing as genotyping markers.
Genetic markers based on PCR-amplified microsatellites have
been extremely important in human genetic studies owing to their
high degree of length polymorphism among individuals in human
populations (
2–
4). The use of fluorescent-labeled microsatellite
markers and fragment analysis by automatic DNA sequencer has
led to widespread applications in studies of population genetics
(
5) and in biomedical researches including human disease mapping
studies for positional cloning (
6,
7), detection of allelic imbalance
or loss of heterozygosity on cancer genome (
8,
9), diagnosis
of expanded triplet repeat loci in several neurodegenerative
diseases (
10) and human identification in forensic analysis
or parentage testing (
11,
12). In large-scale genotyping studies,
although consistent and accurate allele sizing and data handling
required careful selection of markers with high heterozygosity
in selected population, genotyping by using microsatellite markers
remained the most convenient and low cost technology. Since
length polymorphism of microsatellites is population-dependent
and since estimation of allele frequency is essential for successful
linkage analysis (
13,
14), a shared database and resources for
genotyping with microsatellite markers will not only reduce
cost and errors of genotyping but also facilitate disease gene
mapping in human populations. To achieve these aims, the Taiwan
Polymorphie Marker Database (TPMD) was formally launched in
public domain in June 2001. In addition, the Applied Taiwan
Genotyping Consortium (ATGC) was formed from four qualified
laboratories with identical training, experimental protocols
and conventional quality control DNAs (CEPH 1331-01 and 1331-02)
for data expansion of TPMD and from several laboratories for
promoting genetic studies of prevalent inherited disease in
Taiwan. The newly launched TPMD website contains two major sections
including the database for sharing useful microsatellite marker
information and the resources for supporting consistent genotyping
experiments.
|
DATABASE OF MICROSATELLITE MARKERS
|
|---|
Currently, the database contains more than 364 440 allelotyping
data genotyped in Han Chinese of Taiwan from 1425 commonly used
microsatellite markers with average marker density
2.3 cM and
variation types of dinucleotide (856, 60%), trinucleotide (97,
6.8%) and tetranucleotide (470, 33.2%). Majority of microsatellite
markers which are commercially available are obtained from ABI
PRISM Linkage Mapping Set-version 1 and 2 (dinucleotide markers),
and Research Genetics CHLC Human Screening Set/Weber Version
8 and Single Chromosome Human Screening Set (tri- and tetranucleotide
markers). There are 148 (10.4%) markers synthesized in our laboratories
based on UniSTS to meet the needs of specific experiments or
selection process of high heterozygosity markers for constructing
optimal marker set. Two web interfaces with text and map displays
were presented in the TPMD. The text display provides searches
of microsatellite marker either by marker name or by chromosomal
location with hyperlink to UniSTS and to TPMD for detail allelotyping
information such as heterozygosity, range of allele sizes (base
pair), genetic position (cM) and fluorescent labels. To facilitate
marker selection in refine mapping and positional candidate
cloning of disease genes in mapped loci, interfaces for a graphic
map display and retrieving markers from an interesting chromosomal
locus are developed. It features the marker selection by position
in cytogenetic, physical and genetic maps with comparison of
marker heterozygosity in Caucasian, Japanese and Taiwanese populations
(
2,
15,
16). With the integration of other microsatellite markers
from The Center for Medical Genetics at Marshfield Clinic and
DeCODE Genetics into human physical map display (
2,
17), a total
of 7932 commonly used microsatellite markers with average marker
density of 0.4 cM are integrated and should be useful for marker
selection in refine mapping of disease loci and positional candidate
cloning of disease genes.
|
GENOTYPING RESOURCES
|
|---|
To increase the consistency of allele calling and to avoid redundant
microsatellite marker genotyping, we summarized and shared useful
information for facilitating genotyping experiments. In the
resources pages, we provided our protocols for microsatellite
marker genotyping, while a list of markers with atypical variation
types resulted in difficulties of consistent allele calling
in our laboratories, and hence, we recommend TPMD marker set
with 10 cM resolution for optimal genotyping among Taiwanese.
Since marker heterozygosity, especially for heterozygosity >0.7,
is one of the important factors for successful genotyping and
linkage analysis, we compared the distribution of marker heterozygosities
genotyped among Taiwanese, Japanese and Caucasian (
Figure 1).
Our results indicated that the percentages of markers of all
variation types with heterozygosity >0.7 was 82, 73 and 65%
in Caucasian, Japanese and Taiwanese populations, respectively
(
Figure 1A). Similar results were observed in panels of dinucleotide,
trinucleotide and tetranucleotide microsatellite markers genotyped
in the mentioned earlier three populations (
Figure 1B–D).
Indeed, except dinucleotide marker D15S975 with higher heterozygosity
in Taiwanese (0.78) than that in Caucasian (0.44), the remaining
44 microsatellite markers show higher heterozygosity in Caucasian
than that in Taiwanese with a difference of heterozygosity over
0.3 (
Figure 1E). Our results further suggested that the development
of a set of microsatellite markers with high heterozygosity
would facilitate genotyping and genetic studies of human diseases
in Taiwanese. For establishing the optimal set of microsatellite
markers in Taiwanese in use of high-throughput and low cost
protocol, we selected tri- and tetranucleotide markers with
high heterozygosity and well-separated alleles in electrophoresis
as the majority of markers in the optimal set. After careful
experimental evaluation of more than 760 microsatellite markers,
a table with optimal microsatellite marker set contained 363
microsatellite markers (56 dinucleotide, 34 trinucleotide and
273 tetranucleotide markers) with average heterozygosity >0.77
and average marker density of 9.71 cM is included for genotyping
in Taiwanese population. Based on migration of human populations
in Asia, the development of an optimal microsatellite marker
set should be potentially suitable for genotyping in Mongoloid
populations (
18,
19).
View larger version (55K):
[in this window]
[in a new window]
|
Figure 1. Comparison of heterozygosity of microsatellite markers in human populations. The distribution of marker heterozygosity in percentage of total markers (A), dinucleotide repeats (B), trinucleotide repeats (C) and tetranucleotide repeats (D) were shown. The asterisk represents only 19 trinucleotide markers genotyped in Japanese that were available in the literature (16). (E) The 45 microsatellite markers with a difference of heterozygosity over 0.3 in comparison between Caucasian and Taiwanese population.
|
|
|
FUTURE DEVELOPMENT
|
|---|
We aim to expand microsatellite marker genotyping data in TPMD
and increase marker density to 5 cM resolution for optimal set
of microsatellite markers in Taiwanese. The qualified genotyping
data from other populations including aborigines of Taiwan will
be included in the future. With maturation of single nucleotide
polymorphism (SNP) genotyping technologies, we will incorporate
SNP markers genotyped in Taiwanese started from high minor allele
frequency SNP markers.
|
ACKNOWLEDGEMENTS
|
|---|
We are indebted to members in Department of Research Resources
of NHRI for TPMD maintenance. This work was supported by the
National Research Program for Genomic Medicine of National Science
Council and by the intramural funding of National Health Research
Institutes (NHRI). Many authors in Applied Taiwan Genotyping
Consortium (ATGC) received contract grants from Division of
Molecular Genomic Medicine with help from Department of Intramural
Research Affairs of NHRI.
|
Notes
|
|---|
The online version of this article has been published under
an open access model. Users are entitled to use, reproduce,
disseminate, or display the open access version of this article
for non-commercial purposes provided that: the original authorship
is properly and fully attributed; the Journal and Oxford University
Press are attributed as the original place of publication with
the correct citation details given; if an article is subsequently
reproduced or disseminated not in its entirety but only in part
or as a derivative work this must be clearly indicated. For
commercial re-use permissions, please contact
journals.permissions{at}oupjournals.org.
|
REFERENCES
|
|---|
- Lander,E.S., Linton,L.M., Birren,B., Nusbaum,C., Zody,M.C., Baldwin,J., Devon,K., Dewar,K., Doyle,M., FitzHugh,W. et al. ( (2001) ) Initial sequencing and analysis of the human genome. Nature, , 409, , 860–921.[CrossRef][Medline]
.
- Broman,K.W., Murray,J.C., Sheffield,V.C., White,R.L. and Weber,J.L. ( (1998) ) Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am. J. Hum. Genet., , 63, , 861–869.[CrossRef][Web of Science][Medline]
.
- Weissenbach,J., Gyapay,G., Dib,C., Vignal,A., Morissette,J., Millasseau,P., Vaysseix,G. and Lathrop,M. ( (1992) ) A second-generation linkage map of the human genome. Nature, , 359, , 794–801.[CrossRef][Medline]
.
- Gyapay,G., Morissette,J., Vignal,A., Dib,C., Fizames,C., Millasseau,P., Marc,S., Bernardi,G., Lathrop,M. and Weissenbach,J. ( (1994) ) The 1993–94 Genethon human genetic linkage map. Nature Genet., , 7, , 246–339.[CrossRef][Web of Science][Medline]
.
- Schlotterer,C. and Pemberton,J. ( (1994) ) The use of microsatellites for genetic analysis of natural populations. EXS., , 69, , 203–214.[Medline]
.
- Dib,C., Faure,S., Fizames,C., Samson,D., Drouot,N., Vignal,A., Millasseau,P., Marc,S., Hazan,J., Seboun,E. et al. ( (1996) ) A comprehensive genetic map of the human genome based on 5264 microsatellites. Nature, , 380, , 152–154.[CrossRef][Medline]
.
- Chen,W.M., Liu,Y.F., Lin,M.W., Chen,I.C., Lin,P.Y., Lin,G.L., Jou,Y.S., Lin,Y.T., Fann,C.S., Wu,J.Y. et al. ( (2004) ) Autosomal dominant avascular necrosis of femoral head in two taiwanese pedigrees and linkage to chromosome 12q13. Am. J. Hum. Genet., , 75, , 310–317.[CrossRef][Web of Science][Medline]
.
- Mao,L., Schoenberg,M.P., Scicchitano,M., Erozan,Y.S., Merlo,A., Schwab,D. and Sidransky,D. ( (1996) ) Molecular detection of primary bladder cancer by microsatellite analysis. Science, , 271, , 659–662.[Abstract]
.
- Jou,Y.S., Lee,C.S., Chang,Y.H., Hsiao,C.F., Chen,C.F., Chao,C.C., Wu,L.S., Yeh,S.H., Chen,D.S. and Chen,P.J. ( (2004) ) Clustering of minimal deleted regions reveals distinct genetic pathways of human hepatocellular carcinoma. Cancer Res., , 64, , 3030–3036.[Abstract/Free Full Text]
.
- Caskey,C.T., Pizzuti,A., Fu,Y.H., Fenwick,R.G., Jr and Nelson,D.L. ( (1992) ) Triplet repeat mutations in human disease. Science, , 256, , 784–789.[Abstract/Free Full Text]
.
- Edwards,A., Civitello,A., Hammond,H.A. and Caskey,C.T. ( (1991) ) DNA typing and genetic mapping with trimeric and tetrameric tandem repeats. Am. J. Hum. Genet., , 49, , 746–756.[Web of Science][Medline]
.
- Edwards,A., Hammond,H.A., Jin,L., Caskey,C.T. and Chakraborty,R. ( (1992) ) Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics, , 12, , 241–253.[CrossRef][Web of Science][Medline]
.
- Goring,H.H. and Terwilliger,J.D. ( (2000) ) Linkage analysis in the presence of errors II: marker-locus genotyping errors modeled with hypercomplex recombination fractions. Am. J. Hum. Genet., , 66, , 1107–1118.[CrossRef][Web of Science][Medline]
.
- Abecasis,G.R., Cherny,S.S. and Cardon,L.R. ( (2001) ) The impact of genotyping error on family-based analysis of quantitative traits. Eur. J. Hum. Genet., , 9, , 130–134.[CrossRef][Web of Science][Medline]
.
- Ikari,K., Onda,H., Furushima,K., Maeda,S., Harata,S. and Takeda,J. ( (2001) ) Establishment of an optimized set of 406 microsatellite markers covering the whole genome for the Japanese population. J. Hum. Genet., , 46, , 207–210.[CrossRef][Web of Science][Medline]
.
- Mizutani,M., Yamamoto,T., Torii,K., Kawase,H., Yoshimoto,T., Uchihi,R., Tanaka,M., Tamaki,K. and Katsumata,Y. ( (2001) ) Analysis of 168 short tandem repeat loci in the Japanese population, using a screening set for human genetic mapping. J. Hum. Genet., , 46, , 448–455.[CrossRef][Web of Science][Medline]
.
- Kong,A., Gudbjartsson,D.F., Sainz,J., Jonsdottir,G.M., Gudjonsson,S.A., Richardsson,B., Sigurdardottir,S., Barnard,J., Hallbeck,B., Masson,G. et al. ( (2002) ) A high-resolution recombination map of the human genome. Nature Genet., , 31, , 241–247.[CrossRef][Web of Science][Medline]
.
- Cavalli-Sforza,L.L. ( (1997) ) Genes, peoples, and languages. Proc. Natl Acad. Sci. USA, , 94, , 7719–7724.[Abstract/Free Full Text]
.
- Cavalli-Sforza,L.L. ( (1998) ) The DNA revolution in population genetics. Trends Genet., , 14, , 60–65.[CrossRef][Web of Science][Medline]
.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Y. Galperin
The Molecular Biology Database Collection: 2005 update
Nucleic Acids Res.,
January 1, 2005;
33(suppl_1):
D5 - D24.
[Abstract]
[Full Text]
[PDF]
|
|
|
TOP
ABSTRACT
INTRODUCTION