Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans
Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a simi...
| Váldodahkkit: | , , , , , , , , , , , , , , , |
|---|---|
| Materiálatiipa: | Journal article |
| Giella: | English |
| Almmustuhtton: |
Springer Nature
2020
|
| _version_ | 1826269535333777408 |
|---|---|
| author | Wei, W Pagnamenta, AT Gleadall, N Sanchis-Juan, A Stephens, J Broxholme, J Tuna, S Odhams, CA Genomics England Research Consortium NIHR BioResource Fratter, C Turro, E Caulfield, MJ Taylor, JC Rahman, S Chinnery, PF |
| author_facet | Wei, W Pagnamenta, AT Gleadall, N Sanchis-Juan, A Stephens, J Broxholme, J Tuna, S Odhams, CA Genomics England Research Consortium NIHR BioResource Fratter, C Turro, E Caulfield, MJ Taylor, JC Rahman, S Chinnery, PF |
| author_sort | Wei, W |
| collection | OXFORD |
| description | Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans. |
| first_indexed | 2024-03-06T21:26:34Z |
| format | Journal article |
| id | oxford-uuid:434a35c8-fa4d-437f-b58c-79341e86cc6a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:26:34Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:434a35c8-fa4d-437f-b58c-79341e86cc6a2022-03-26T14:54:32ZNuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humansJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:434a35c8-fa4d-437f-b58c-79341e86cc6aEnglishSymplectic ElementsSpringer Nature2020Wei, WPagnamenta, ATGleadall, NSanchis-Juan, AStephens, JBroxholme, JTuna, SOdhams, CAGenomics England Research ConsortiumNIHR BioResourceFratter, CTurro, ECaulfield, MJTaylor, JCRahman, SChinnery, PFSeveral strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans. |
| spellingShingle | Wei, W Pagnamenta, AT Gleadall, N Sanchis-Juan, A Stephens, J Broxholme, J Tuna, S Odhams, CA Genomics England Research Consortium NIHR BioResource Fratter, C Turro, E Caulfield, MJ Taylor, JC Rahman, S Chinnery, PF Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans |
| title | Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans |
| title_full | Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans |
| title_fullStr | Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans |
| title_full_unstemmed | Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans |
| title_short | Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans |
| title_sort | nuclear mitochondrial dna segments resemble paternally inherited mitochondrial dna in humans |
| work_keys_str_mv | AT weiw nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT pagnamentaat nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT gleadalln nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT sanchisjuana nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT stephensj nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT broxholmej nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT tunas nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT odhamsca nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT genomicsenglandresearchconsortium nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT nihrbioresource nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT fratterc nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT turroe nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT caulfieldmj nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT taylorjc nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT rahmans nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans AT chinnerypf nuclearmitochondrialdnasegmentsresemblepaternallyinheritedmitochondrialdnainhumans |