
미토콘드리아 DNA 하플로그룹 명명법의 복잡성과 비표준화로 인해 유전 데이터 분석 및 해석에 편향이 발생할 수 있다.


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Population-based studies of human mitochondrial genetic diversity often require the classification of mitochondrial DNA (mtDNA) haplotypes into more than 5400 described haplogroups, and further grouping those into hierarchically higher haplogroups. Such secondary haplogroup groupings (e.g., “macro-haplogroups”) vary across studies, as they depend on the sample quality, technical factors of haplogroup calling, the aims of the study, and the researchers’ understanding of the mtDNA haplogroup nomenclature. Retention of historical nomenclature coupled with a growing number of newly described mtDNA lineages results in increasingly complex and inconsistent nomenclature that does not reflect phylogeny well. This “clutter” leaves room for grouping errors and inconsistencies across scientific publications, especially when the haplogroup names are used as a proxy for secondary groupings, and represents a source for scientific misinterpretation.

Here we explore the effects of phylogenetically insensitive secondary mtDNA haplogroup groupings, and the lack of standardized secondary haplogroup groupings on downstream analyses and interpretation of genetic data. We demonstrate that frequency-based analyses produce inconsistent results when different secondary mtDNA groupings are applied, and thus allow for vastly different interpretations of the same genetic data. The lack of guidelines and recommendations on how to choose appropriate secondary haplogroup groupings presents an issue for the interpretation of results, as well as their comparison and reproducibility across studies.

To reduce biases originating from arbitrarily defined secondary nomenclature-based groupings, we suggest that future updates of mtDNA phylogenies aimed for the use in mtDNA haplogroup nomenclature should also provide well-defined and standardized sets of phylogenetically meaningful algorithm-based secondary haplogroup groupings such as “macro-haplogroups”, “meso-haplogroups”, and “micro-haplogroups”. Ideally, each of the secondary haplogroup grouping levels should be informative about different human population history events. Those phylogenetically informative levels of haplogroup groupings can be easily defined using TreeCluster , and then implemented into haplogroup callers such as HaploGrep3 . This would foster reproducibility across studies, provide a grouping standard for population-based studies, and reduce errors associated with haplogroup nomenclatures in future studies.

### Competing Interest Statement

The authors have declared no competing interest.

*   NBG
    :   Nomenclature-Based Groupings
    SC
    :   Single Character grouping
    SCL
    :   Single Character and L with one digit grouping
    ABG
    :   Algorithm-Based Groupings
    mtDNA
    :   Mitochondrial DNA
    rCRS
    :   The revised Cambridge Reference Sequence
    RSRS
    :   The Reconstructed Sapiens Reference Sequence
    MDS
    :   Multidimensional scaling
    CA
    :   Correspondence analysis
    rhb_01 
    :   Results of rhierBAPS level 1
    rhb_02 
    :   Results of rhierBAPS level 2
    rhb_03 
    :   Results of rhierBAPS level 3
    tc_0.006 
    :   Results of TreeCluster with the threshold value of 0.006
    tc_0.005 
    :   Results of TreeCluster with the threshold value of 0.005
    tc_0.004 
    :   Results of TreeCluster with the threshold value of 0.004
    tc_0.003 
    :   Results of TreeCluster with the threshold value of 0.003

*   ACB
    :   African Caribbean in Barbados
    ASW
    :   African Ancestry in SW USA
    MSL
    :   Mende in Sierra Leone
    GWD
    :   Gambian in Western Division – Mandinka
    ESN
    :   Esan in Nigeria
    YRI
    :   Yoruba in Ibadan, Nigeria
    LWK
    :   Luhya in Webuye, Kenya

mtDNA “Nomenclutter” and its Consequences on the Interpretation of Genetic Data

미토콘드리아-dna-명명-혼란-과-유전-데이터-해석에-미치는-영향


미토콘드리아 DNA "명명 혼란"과 유전 데이터 해석에 미치는 영향
