1. 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

2. 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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4. Polymorphic Markers Heterozygosity H= 1- (p12 + p22 + p32 + …)
Polymorphism information content (PIC)
PIC = 1-  pi2 -   2pi2pj2
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6. Microsatellite Markers
Types:
di- (CA)n,
tri- (CAG)n,
tetra- (GATA)n nucleotide repeats.
Evenly distributed through genome.
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7. Microsatellite Markers
Primer 1 CA CA CA
Primer 2 CA CA CA CA CA CA CA CA CA CA CA CA CA CA CA
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8. 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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YMGC Genotyping Core

9. Applications
Linkage mapping and association study (linkage disequilibrium)
Loss of heterozygosity
Microsatellite instability
Forensic application
Paternity identification
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10. Collins FS. (1992) Nature genetics 1:3-6
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11. Collins FS. (1992) Nature genetics 1:3-6
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12. Linkage Mapping for Disease Genes
Linkage analysis
(Lod score method)
Allele-sharing methods
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13. Linkage Analysis Family
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14. Allele-Sharing MethodAC AB AC BC AB CD BC BC AC AB AD BC
IBD = 0
IBD = 2
IBD = 1
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15. Loss of Heterozygosity
Loss of one allele at a heterozygous locus in a tumour cell, resulting in a homozygous genotype.
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17. Microsatellite Instability
Microsatellite instability is numerous or aberrant allele at a microsatellite locus.
Many tumours show microsatellite instability.
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19. Microsatellite Marker Databases
GDB:
Marshfield:
CHLC (Cooperative Human Linkage Center):
Genethon:
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20. GDB
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21. GDB
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22. GDB
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23. GDB
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24. GDB
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25. GDB
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26. GDB
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27. GDB
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28. GDB
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29. GDB
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30. GDB
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31. GDB
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32. GDB
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33. GDB
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34. GDB
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35. GDB
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36. GDB
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37. GDB
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38. Marshfield
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39. Marshfield
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40. Marshfield
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41. Marshfield
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42. Marshfield
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43. Marshfield
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44. Marshfield
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45. Marshfield
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46. Marshfield
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47. CHLC
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48. CHLC
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49. CHLC
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50. CHLC
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51. CHLC
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52. CHLC
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53. Genethon
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54. Microsatellite Marker Databases
NCBI:
CEPH (Centre d’Etude du Polymorphisme Humain):
Utah:
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55. NCBI
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56. NCBI
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57. CEPH
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58. CEPH
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59. CEPH
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60. Standardized Genotype Data
CEPH
CEPH
CEPH
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61. ABI PRISM Linkage Mapping Set
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62. ABI PRISM Linkage Mapping Set
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63. ABI PRISM Linkage Mapping Set
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64. ABI PRISM Linkage Mapping Set
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YMGC Genotyping Core