Searching Microsatellite Markers for Mapping a Disease Gene 林明薇
Download
Report
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)
Jan, 2003
YMGC Genotyping Core
Jan, 2003
YMGC Genotyping Core
Polymorphic Markers
• Heterozygosity
H= 1- (p12 + p22 + p32 + …)
• Polymorphism information content (PIC)
PIC = 1- pi2 - 2pi2pj2
Jan, 2003
YMGC Genotyping Core
Jan, 2003
YMGC Genotyping Core
Microsatellite Markers
•Types:
di- (CA)n,
tri- (CAG)n,
tetra- (GATA)n nucleotide
repeats.
•Evenly distributed through
genome.
Jan, 2003
YMGC Genotyping Core
Microsatellite Markers
Primer 1
Jan, 2003
Primer 2
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
CA
YMGC Genotyping Core
Genotyping Results
D13S121- dinucleotide
D13S770 - trinucleotide
Child 1
Child 1
Child 2
Child 2
Child 3
Child 3
Father
Father
Mother
Mother
Jan, 2003
YMGC Genotyping Core
Applications
•Linkage mapping and
association study
(linkage disequilibrium)
•Loss of heterozygosity
•Microsatellite instability
•Forensic application
•Paternity identification
Jan, 2003
YMGC Genotyping Core
Collins FS. (1992) Nature genetics 1:3-6
Jan, 2003
YMGC Genotyping Core
Collins FS. (1992) Nature genetics 1:3-6
Jan, 2003
YMGC Genotyping Core
Linkage Mapping for
Disease Genes
•Linkage analysis
(Lod score method)
•Allele-sharing
methods
Jan, 2003
YMGC Genotyping Core
Linkage Analysis Family
Jan, 2003
YMGC Genotyping Core
Allele-Sharing Method
AC
AB
AC
BC
AB
CD
BC
BC
AC
AB
AD
BC
IBD = 2
Jan, 2003
IBD = 1
IBD = 0
YMGC Genotyping Core
Loss of Heterozygosity
Loss of one allele at a
heterozygous locus in a
tumour cell, resulting in a
homozygous genotype.
Jan, 2003
YMGC Genotyping Core
Jan, 2003
YMGC Genotyping Core
Microsatellite
Instability
•Microsatellite instability is
numerous or aberrant allele at
a microsatellite locus.
•Many tumours show
microsatellite instability.
Jan, 2003
YMGC Genotyping Core
Jan, 2003
YMGC Genotyping Core
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
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
GDB
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
Marshfield
Jan, 2003
YMGC Genotyping Core
CHLC
Jan, 2003
YMGC Genotyping Core
CHLC
Jan, 2003
YMGC Genotyping Core
CHLC
Jan, 2003
YMGC Genotyping Core
CHLC
Jan, 2003
YMGC Genotyping Core
CHLC
Jan, 2003
YMGC Genotyping Core
CHLC
Jan, 2003
YMGC Genotyping Core
Genethon
Jan, 2003
YMGC Genotyping Core
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
Jan, 2003
YMGC Genotyping Core
NCBI
Jan, 2003
YMGC Genotyping Core
NCBI
Jan, 2003
YMGC Genotyping Core
CEPH
Jan, 2003
YMGC Genotyping Core
CEPH
Jan, 2003
YMGC Genotyping Core
CEPH
Jan, 2003
YMGC Genotyping Core
Standardized
Genotype Data
• CEPH 1331-01
• CEPH 1331-02
• CEPH 1347-02
Jan, 2003
YMGC Genotyping Core
ABI PRISM Linkage
Mapping Set
• http://home.appliedbiosystems.
com/
Jan, 2003
YMGC Genotyping Core
ABI PRISM Linkage Mapping Set
Jan, 2003
YMGC Genotyping Core
ABI PRISM Linkage Mapping Set
Jan, 2003
YMGC Genotyping Core
ABI PRISM Linkage Mapping Set
Jan, 2003
YMGC Genotyping Core