GGAW - Oct, 2001 M-W LIN Searching Microsatellite Markers for Mapping a Disease Gene 林明薇...
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Transcript of GGAW - Oct, 2001 M-W LIN Searching Microsatellite Markers for Mapping a Disease Gene 林明薇...
![Page 1: GGAW - Oct, 2001 M-W LIN 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.](https://reader030.fdocuments.net/reader030/viewer/2022012819/56649f565503460f94c798d1/html5/thumbnails/1.jpg)
GGAW - Oct, 2001 M-W LIN
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
![Page 2: GGAW - Oct, 2001 M-W LIN 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.](https://reader030.fdocuments.net/reader030/viewer/2022012819/56649f565503460f94c798d1/html5/thumbnails/2.jpg)
GGAW - Oct, 2001 M-W LIN
Genetic Markers•Protein marker
blood group, HLA tissue types…etc..
•DNA markerRFLPs (restriction fragment length
polymorphisms)Minisatellites (VNTR - variable
number tandem repeats)Microsatellites (STR - short tandem
repeats)SNPs (single nucleotide
polymorphisms)
![Page 3: GGAW - Oct, 2001 M-W LIN 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.](https://reader030.fdocuments.net/reader030/viewer/2022012819/56649f565503460f94c798d1/html5/thumbnails/3.jpg)
GGAW - Oct, 2001 M-W LIN
Microsatellite Markers
•Types:di- (CA)n,tri- (CAG)n,tetra- (GATA)n nucleotide repeats.
•Evenly distributed through genome.
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GGAW - Oct, 2001 M-W LIN
Microsatellite Markers
CA
CA CA
Primer 1
Primer 2
CA
CA CA CA
CA
CA CA CA CA
CA
CA CA CA CA CA
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GGAW - Oct, 2001 M-W LIN
Genotyping Results
Child 1
Child 2
Child 3
Father
Mother
Child 1
Child 2
Child 3
Father
Mother
D13S121- dinucleotide
D13S770 - trinucleotide
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GGAW - Oct, 2001 M-W LIN
Applications•Linkage mapping and association study (linkage disequilibrium)
•Loss of heterozygosity•Microsatellite instability•Forensic application•Paternity identification
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GGAW - Oct, 2001 M-W LIN
![Page 8: GGAW - Oct, 2001 M-W LIN 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.](https://reader030.fdocuments.net/reader030/viewer/2022012819/56649f565503460f94c798d1/html5/thumbnails/8.jpg)
GGAW - Oct, 2001 M-W LIN
![Page 9: GGAW - Oct, 2001 M-W LIN 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.](https://reader030.fdocuments.net/reader030/viewer/2022012819/56649f565503460f94c798d1/html5/thumbnails/9.jpg)
GGAW - Oct, 2001 M-W LIN
Linkage Mapping for Disease Genes
•Linkage analysis (Lod score method)•Allele-sharing methods
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GGAW - Oct, 2001 M-W LIN
Linkage Analysis Family
BD BCAC BC
BE AF
AB CD
AD AD
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GGAW - Oct, 2001 M-W LIN
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GGAW - Oct, 2001 M-W LIN
LinkageLinkage describes the phenomenon whereby allele at neighbouring loci are close to one another on the same chromosome, they will be transmitted together more frequently than chance.
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GGAW - Oct, 2001 M-W LIN
Recombinant Gametes
Crossing over between
two neighbouring loci
will produce
recombinant gametes.
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GGAW - Oct, 2001 M-W LIN
Recombination Fraction
Recombination fraction (θ) = number of recombinant gametes------------------------------------------
total gametes
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GGAW - Oct, 2001 M-W LIN
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GGAW - Oct, 2001 M-W LIN
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GGAW - Oct, 2001 M-W LIN
Recombination Fraction
•Recombination fraction is a measure of genetic distance.
•1cM=1% chance of recombination between two loci.
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GGAW - Oct, 2001 M-W LIN
Statistical Significance of the
Lod Scorelod score > 3: evidence of linkage
2 < lod score < 3: suggestive evidence of
linkage
-2 < lod score < 2: uninformative of
linkage
lod score < -2: exclusion of linkage
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GGAW - Oct, 2001 M-W LIN
Loss of Heterozygosity
Loss of one allele at a heterozygous locus in
a tumour cell, resulting in a homozygous genotype.
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GGAW - Oct, 2001 M-W LIN
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GGAW - Oct, 2001 M-W LIN
Microsatellite Instability
•Microsatellite instability is numerous or aberrant allele at a microsatellite locus.
•Many tumours show
microsatellite instability.
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GGAW - Oct, 2001 M-W LIN
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GGAW - Oct, 2001 M-W LIN
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
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
GDB
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
Marshfield
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GGAW - Oct, 2001 M-W LIN
CHLC
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GGAW - Oct, 2001 M-W LIN
CHLC
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GGAW - Oct, 2001 M-W LIN
CHLC
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GGAW - Oct, 2001 M-W LIN
CHLC
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GGAW - Oct, 2001 M-W LIN
CHLC
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GGAW - Oct, 2001 M-W LIN
CHLC
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GGAW - Oct, 2001 M-W LIN
Genethon
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GGAW - Oct, 2001 M-W LIN
Genethon
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GGAW - Oct, 2001 M-W LIN
Genethon
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GGAW - Oct, 2001 M-W LIN
Microsatellite Marker Databases
• CEPH (Centre d’Etude du Polymorphisme Humain): http://www.cephb.fr
• Utah: http://www.genetics.utah.edu/home.html
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GGAW - Oct, 2001 M-W LIN
CEPH
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GGAW - Oct, 2001 M-W LIN
CEPH
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GGAW - Oct, 2001 M-W LIN
CEPH
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GGAW - Oct, 2001 M-W LIN
Standardized Genotype Data
• CEPH 1331-01
• CEPH 1331-02
• CEPH 1347-02
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GGAW - Oct, 2001 M-W LIN
NHRI Databases• GDB mirror site
http://gdb.nhri.org.tw/
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GGAW - Oct, 2001 M-W LIN
Successful Examples• Cystic fibrosis
• Huntington disease
• Early onset breast cancer (BRCA1, BRCA2)
• Alzheimer disease (chr14, chr1)
• Maturity-onset diabetes of the young (MODY) (chr12)
• ...