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 CA CA CA Primer 2 CA CA CA CA CA CA CA CA CA CA CA CA CA CA CA Jan, 2003 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 = 0 IBD = 2 IBD = 1 Jan, 2003 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.html 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