Linkage Studies (1a).

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Presentation transcript:

Linkage Studies (1a)

Linkage Studies (1b)

Power of 595 independent sib pairs (Koller et al Power of 595 independent sib pairs (Koller et al. 2000) and 53 pedigrees composed of 630 individuals (Deng et al. 2002). A: recombination fraction=0 B: recombination fraction=0.05.

Linkage Studies (2)

Linkage Studies (3)

Linkage Studies (4)

Linkage Studies (5)

Sib pairs Required to Achieve 80% Power (at LOD 3.0) Comments:

QTL Mapping in Mice

QTLs for Animal Models with Putative Homologous Human Location

QTLs for Animal Models with Putative Homologous Human Location

QTLs for Animal Models with Putative Homologous Human Location

QTLs for Animal Models with Putative Homologous Human Location

Fine Mapping (~30cM to ~1 cM) (Deng et al Fine Mapping (~30cM to ~1 cM) (Deng et al. 2000) Exclusion Mapping (Deng et al., 2001)

What phenotypes to study?

Correlations between two complex traits

Limitation of studying risk factors only (1) NIDDM (Ghosh et al. 2000): chromosomes 20, 11, 2, 10 and 6. Risk factors (Watanabe et al. 2000): chromosomes 3 (fasting C-peptide/glucose), 10 (acute insulin response), 13 (BMI and 2-h insulin), 17 and 19 (empirical insulin-resistance index).

Limitation of studying risk factors only (2) Myocardial infarction (Broeckel et al., 2002): Chromosome 14. Risk factors (Broeckel et al., 2002): Chromosomes 1 and 6 (lipoprotein a), 14,17 (LDL cholesterol concentrations), 1 (HDL cholesterol concentrations) , 9 (triglyceride concentration), 6 (type II diabetes), 6 (systolic hypertention), 1 (diastolic hypertention).

DNA microarray studies

DNA microarray studies: Examples Identification of 9 novel genes and ESTs induced in murine osteoblasts during their differentiation from mesenchymal progenitor cells (Vaes et al., 2002).

Proteomics ~30,000 genes, 1.5 million proteins. Analyzing functions of gene products (large-scale identifying or localizing proteins and studies of protein-protein interactions). Linking gene expression to cell metabolism and function and to genetic maps.

Acknowledgement

Thank you!