## Mitochondrial genomes hg19是University of California at Santa Cruz (UCSC)整理的，因他們的Genome Browser是當時最好用的軟體，hg19版本廣為流傳。 hg19版本是UCSC基於GRCh37版本，更動某些contig名稱，因此除核心染色體外，其他contig的編碼跟GRCh37不同。 粒線體版本在hg19採用NC_001807.4(現已被NCBI移除) ![](https://i.imgur.com/m1WnaMM.png) :small_blue_diamond: Blastn for Sequence in hg19 (UCSC) ![image](https://hackmd.io/_uploads/B10m9mBd6.png) 而hg38/GRCh38 及GRCh37採NC_012920.1 :small_blue_diamond: Blastn for Sequence in hg38 (GRCh38) ![image](https://hackmd.io/_uploads/ByrHjQHua.png) ![image](https://hackmd.io/_uploads/ryg66mS_6.png) 將兩組粒線體版本做Pair-wise blast的結果，可以看到identities上有42個差異。 ![image](https://hackmd.io/_uploads/By2AQEH_6.png) :::success Conclusion: It is recommended to use NC_012920.1 as reference of Mitochondrial DNA because it has been widely used in most of database. ::: --- ## Heteroplasmic level 1. Heteroplasmy (異質性) is defined as a state in which more than one chloroplast (葉綠體) or mitochondrial (粒線體) genotype occurs in an organism. 2. In fact, heteroplasmy levels often vary even between the cells or somatic tissues of the same individual, leading to situations where only specific cells, tissues, or organs are affected by mitochondrial dysfunction. 3. Instead of the discrete allele frequencies of 0%, 50%, or 100% observed for alleles of nuclear genes, allele frequencies for mtDNA loci have a continuous distribution ranging from 0% to 100% (“homoplasmy”). 4. The mitochondria, and thus mitochondrial DNA, are passed exclusively from mother to offspring through the egg cell. ![image](https://hackmd.io/_uploads/B1BUzBrO6.png) --- ## Interpretation HmtDB MtSNPscore 1. MitoMap (https://www.mitomap.org/) - Comprehensive database of mtDNA variations and mutations - Provides functional annotations and disease associations 2. HmtVar (https://www.hmtvar.uniba.it/) - Annotates human mitochondrial variants - Offers pathogenicity predictions and population frequency data 3. MSeqDR (https://mseqdr.org/) - Mitochondrial disease sequence data resource - Includes various tools for mtDNA analysis and annotation 4. MToolBox (https://github.com/mitoNGS/MToolBox) - Web-based pipeline for mtDNA analysis - Performs variant calling, heteroplasmy detection, and haplogroup assignment 5. Mitomaster (https://www.mitomap.org/foswiki/bin/view/MITOMASTER/WebHome) - Part of MITOMAP, offers various analysis tools - Provides sequence and variant analysis features 6. MitoTIP (https://www.mitimpact.css-mendel.it/) - Predicts pathogenicity of novel mitochondrial tRNA variations 7. MitImpact (https://mitimpact.css-mendel.it/) - Focuses on protein-coding mtDNA variants - Provides pathogenicity predictions and functional impact assessments 8. gnomAD 9. clinvar --- ## References https://www.prismabiotech.com.tw/post/dragen%E4%B8%8Agrch37%E5%8F%83%E8%80%83%E5%BA%8F%E5%88%97%E7%89%88%E6%9C%AC%E7%9A%84%E5%B7%AE%E5%88%A5 https://sapac.support.illumina.com/sequencing/sequencing_software/igenome.html https://pubmed.ncbi.nlm.nih.gov/32906214/ https://academic.oup.com/clinchem/article/58/9/1322/5620749 https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/heteroplasmy ###### tags: `genomics`