# Haplogroup Structure and Genetic Variation Analyses of Mitochondrial Genome SNPs in the Iranian Population

## TL;DR

This study analyzed mitochondrial DNA in the Iranian population to understand genetic variation and haplogroup distribution across four ethnic groups.

## Contribution

The study provides new insights into mtDNA haplogroup frequencies and genetic diversity in Iranians using targeted sequencing and WES comparisons.

## Key findings

- Haplogroups U and H were the most frequent in the Iranian population, with frequencies of 22.4% and 20.3%, respectively.
- PCA analysis showed overlapping diversity with no distinct separation among the four ethnic groups.
- Targeted mtDNA sequencing detected more variants than WES, suggesting it is a more reliable method for variant detection.

## Abstract

Mitochondrial DNA (mtDNA) is a valuable marker for population studies and forensic investigations. Recent advancements in massively parallel sequencing technologies enable whole mitochondrial genome sequencing. This study collected blood samples from unrelated Iranian participants from four ethnic groups: Persian, Kurd, Lur, and Azeri. We mapped mtDNA haplogroups according to genetic ancestry and investigated the ethnic similarities within the Iranian population.

Complete mtDNA sequences were generated with targeted mtDNA sequencing method and haplogroups were determined on the base of mitogenome polymorphisms. Additionally, we used data from the whole exome sequencing (WES) of the current samples to compare the variants identified by two different mitochondrial testing methods. Principal component analysis (PCA) calculations were performed using the R software to determine diversity between unrelated individuals of various ethnicities.

A total of 129 sub-haplogroups were identified in 15 main haplogroups. The findings revealed high frequencies of haplogroups U and H (22.4% and 20.3%, respectively) in the Iranian population. The PCA scatter plots revealed overlapping diversity, with no distinct trends separating the groups in these four groups within the Iranian population. In the present samples, the WES method identified only 57.8% of the variants detected by the targeted mtDNA sequencing method.

Variant studies do not show much difference, which indicate a small genetic difference between the central ethnic groups of Iran. Furthermore, comparing the targeted whole mitochondrial genome to mitochondrial data from WES in our study samples highlights the notion that targeted entire mitochondrial genome is a gold standard method for variant detection.