Transcript Searching Microsatellite Markers for Mapping a Disease Gene 林明薇

Searching Microsatellite
Markers for Mapping a
Disease Gene
林明薇 Ming-Wei Lin, PhD
陽明大學醫學系家庭醫學科
台北榮民總醫院教學研究部
Jan, 2003
YMGC Genotyping Core
Genetic Markers
• Protein marker
 blood group, HLA tissue types…etc..
• DNA marker
RFLPs (restriction fragment length
polymorphisms)
Minisatellites (VNTR - variable number
tandem repeats)
Microsatellites (STR - short tandem
repeats)
SNPs (single nucleotide polymorphisms)
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Polymorphic Markers
• Heterozygosity
 H= 1- (p12 + p22 + p32 + …)
• Polymorphism information content (PIC)
PIC = 1-  pi2 -   2pi2pj2
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Microsatellite Markers
•Types:
di- (CA)n,
tri- (CAG)n,
tetra- (GATA)n nucleotide
repeats.
•Evenly distributed through
genome.
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Microsatellite Markers
Primer 1
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Primer 2
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
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Genotyping Results
D13S121- dinucleotide
D13S770 - trinucleotide
Child 1
Child 1
Child 2
Child 2
Child 3
Child 3
Father
Father
Mother
Mother
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Applications
•Linkage mapping and
association study
(linkage disequilibrium)
•Loss of heterozygosity
•Microsatellite instability
•Forensic application
•Paternity identification
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Collins FS. (1992) Nature genetics 1:3-6
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Collins FS. (1992) Nature genetics 1:3-6
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Linkage Mapping for
Disease Genes
•Linkage analysis
(Lod score method)
•Allele-sharing
methods
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Linkage Analysis Family
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Allele-Sharing Method
AC
AB
AC
BC
AB
CD
BC
BC
AC
AB
AD
BC
IBD = 2
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IBD = 1
IBD = 0
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Loss of Heterozygosity
Loss of one allele at a
heterozygous locus in a
tumour cell, resulting in a
homozygous genotype.
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Microsatellite
Instability
•Microsatellite instability is
numerous or aberrant allele at
a microsatellite locus.
•Many tumours show
microsatellite instability.
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Microsatellite Marker
Databases
• GDB: http://www.gdb.org
• Marshfield:
http://research.marshfieldclinic.org/genetics/
• CHLC (Cooperative Human Linkage
Center): http:/www.chlc.org
• Genethon:
http://www.genethon.fr/genethon_en.ht
ml
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GDB
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GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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YMGC Genotyping Core
GDB
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GDB
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Marshfield
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Marshfield
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Marshfield
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Marshfield
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YMGC Genotyping Core
Marshfield
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YMGC Genotyping Core
Marshfield
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YMGC Genotyping Core
Marshfield
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YMGC Genotyping Core
Marshfield
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YMGC Genotyping Core
Marshfield
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YMGC Genotyping Core
CHLC
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YMGC Genotyping Core
CHLC
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YMGC Genotyping Core
CHLC
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YMGC Genotyping Core
CHLC
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YMGC Genotyping Core
CHLC
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CHLC
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Genethon
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Microsatellite Marker
Databases
• NCBI: http://www.ncbi.nlm.nih.gov/
• CEPH (Centre d’Etude du
Polymorphisme Humain):
http://www.cephb.fr
• Utah:
http://www.genetics.utah.edu/home.
html
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NCBI
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NCBI
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CEPH
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CEPH
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CEPH
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Standardized
Genotype Data
• CEPH 1331-01
• CEPH 1331-02
• CEPH 1347-02
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ABI PRISM Linkage
Mapping Set
• http://home.appliedbiosystems.
com/
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ABI PRISM Linkage Mapping Set
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YMGC Genotyping Core
ABI PRISM Linkage Mapping Set
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YMGC Genotyping Core
ABI PRISM Linkage Mapping Set
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YMGC Genotyping Core