Common variation in human mitochondrial DNA
The human mitochondrial genome is only 16-kb long and is maternally inherited. To identify common SNPs in the coding region of human mtDNA, we created a catalogue of variable sites from >1,200 publicly available mtDNA sequences in GenBank and MitoKor (see Herrnstadt et al., AJHG, 2002), originating from European (n=928), Asian (n=238) and African (n=87) samples. From the alignment of these 928 European sequences, we identified 144 common SNPs with ≥1% frequency and 64 tag SNPs to capture them with r2 ≥ 0.8.
We encourage everyone to consult the Mitomap resource for further information about mitochondrial genetic variation.
This is a project led by Richa Saxena and Paul de Bakker.
- alignment of the sequences (PIR format)
- polymorphic sites
- allele frequencies
- reference panel for European samples (Nick Patterson format) and accompanying marker information file. The listed SNP positions are according to the revised Cambridge reference sequence. Here is the mapping between rCRS and NC001807.4 used by dbSNP.
- 64 tag SNPs to capture the common variants (with >1% frequency) in European samples, and the corresponding statistical tests (here in Haploview format) to be performed in the association analysis.
- FASTA sequences for the 64 mtDNA assays
- Sequenom HME primers and probes for the 64 mtDNA assays (10 pools)
a. All assays are validated and display maternal inheritance of the rarer allele
b. mt13879, mt14470, mt15218, mt15884 and mt10398 are tri-allelic, and only the two most common alleles are captured by the HME assays
- Newer Sequenom iPLEX primers and probes for the 64 mtDNA assays (3 iPLEX pools + 1 HME pool)
a. All assays are validated and display maternal inheritance of the rarer allele.
b. mt13879, mt14470, mt15218, mt15884 and mt10398 are tri-allelic, and all three alleles should be captured by the iPLEX assays.
c. The assay for mt13879 is included twice (both in iPLEX and the single HME pool)
d. Extra assays for markers common in mtDNA of Asian and Native American origin (mt5178, mt1736) and of African origin (mt825, mt663, mt9221) are included.
e. Extra assays for 3 additional SNPs not in the original 64 mtDNA set (mt15904, mt10398 and common D-loop variant mt16189) are included.
R. Saxena, P.I.W. de Bakker, K. Synger, V. Mootha, N. Burtt, J.N. Hirschhorn, D. Gaudet, D. Isomaa, M.J. Daly, L. Groop, K.G. Ardlie, D. Altshuler (2006) Comprehensive association testing of common mitochondrial DNA variation in metabolic disease. American Journal of Human Genetics. 79: 54-61