Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia.
Autosomal recessive conditions are often associated with homozygous mutations showing common ancestral origins and are frequently linked to consanguinity. However, an increasing number of compound heterozygotes are found in diverse, admixed populations. Oculocutaneous albinism (OCA) is a recessive c...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0313777 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846161731429072896 |
|---|---|
| author | Wilmer A Cárdenas Andrew B Conley Shashwat Deepali Nagar Diana L Núñez-Ríos I King Jordan María Claudia Lattig |
| author_facet | Wilmer A Cárdenas Andrew B Conley Shashwat Deepali Nagar Diana L Núñez-Ríos I King Jordan María Claudia Lattig |
| author_sort | Wilmer A Cárdenas |
| collection | DOAJ |
| description | Autosomal recessive conditions are often associated with homozygous mutations showing common ancestral origins and are frequently linked to consanguinity. However, an increasing number of compound heterozygotes are found in diverse, admixed populations. Oculocutaneous albinism (OCA) is a recessive condition caused mainly by mutations in the TYR and OCA2 genes involved in skin pigmentation. We previously screened the TYR and OCA2 genes in Colombian OCA families, identifying both known and novel mutations. Affected family members were found to be either homozygous or compound heterozygous for these gene mutations. Compound heterozygosity, where two different recessive alleles inherited from each parent lead to the expression of an autosomal recessive trait, poses a challenge in genetic diagnosis. Estimating the ancestry of these disease-associated variants, in conjunction with understanding the colonization history of admixed populations, can enhance the precision of association mapping in genetic studies. The aim of this study was to determine the ancestral origins of TYR and OCA2 mutations for OCA patients from two populations located in the Andes region of Colombia-Altiplano Cundiboyacense and Marinilla-Santuario. Comparison of OCA patients, and their unaffected relatives, with global reference populations showed a pattern of European and Native American admixture, with little African ancestry, for these two populations. Mutation-bearing TYR and OCA2 haplotypes from Colombian OCA patients were compared against haplotypes from Spanish, Native American, and Sephardic Jewish reference populations to infer their ancestral origins. For 12 OCA1 patients from the Altiplano Cundiboyacense region, 21 out of 24 mutated TYR haplotypes show Spanish origins, two show Native American origins, and one shows a Sephardic Jewish origin. The two Native American TYR haplotypes, and the single Sephardic Jewish haplotype, are all found in compound heterozygote patients, paired with the predominant Spanish TYR haplotype G47D. OCA in these three patients is a result of genetic admixture that brought together disease-causing mutations with distinct ancestral origins. Both OCA2 patients from the Marinilla-Santuario region show homozygous OCA2 mutations with a Spanish origin. These findings underscore the complexity of the genetic architecture of Mendelian disease in admixed American populations, with both consanguinity and admixture contributing to the risk of autosomal recessive OCA in Colombia. |
| format | Article |
| id | doaj-art-1fdc6053b496486b8e06da9c7c68e542 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-1fdc6053b496486b8e06da9c7c68e5422024-11-21T05:30:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011911e031377710.1371/journal.pone.0313777Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia.Wilmer A CárdenasAndrew B ConleyShashwat Deepali NagarDiana L Núñez-RíosI King JordanMaría Claudia LattigAutosomal recessive conditions are often associated with homozygous mutations showing common ancestral origins and are frequently linked to consanguinity. However, an increasing number of compound heterozygotes are found in diverse, admixed populations. Oculocutaneous albinism (OCA) is a recessive condition caused mainly by mutations in the TYR and OCA2 genes involved in skin pigmentation. We previously screened the TYR and OCA2 genes in Colombian OCA families, identifying both known and novel mutations. Affected family members were found to be either homozygous or compound heterozygous for these gene mutations. Compound heterozygosity, where two different recessive alleles inherited from each parent lead to the expression of an autosomal recessive trait, poses a challenge in genetic diagnosis. Estimating the ancestry of these disease-associated variants, in conjunction with understanding the colonization history of admixed populations, can enhance the precision of association mapping in genetic studies. The aim of this study was to determine the ancestral origins of TYR and OCA2 mutations for OCA patients from two populations located in the Andes region of Colombia-Altiplano Cundiboyacense and Marinilla-Santuario. Comparison of OCA patients, and their unaffected relatives, with global reference populations showed a pattern of European and Native American admixture, with little African ancestry, for these two populations. Mutation-bearing TYR and OCA2 haplotypes from Colombian OCA patients were compared against haplotypes from Spanish, Native American, and Sephardic Jewish reference populations to infer their ancestral origins. For 12 OCA1 patients from the Altiplano Cundiboyacense region, 21 out of 24 mutated TYR haplotypes show Spanish origins, two show Native American origins, and one shows a Sephardic Jewish origin. The two Native American TYR haplotypes, and the single Sephardic Jewish haplotype, are all found in compound heterozygote patients, paired with the predominant Spanish TYR haplotype G47D. OCA in these three patients is a result of genetic admixture that brought together disease-causing mutations with distinct ancestral origins. Both OCA2 patients from the Marinilla-Santuario region show homozygous OCA2 mutations with a Spanish origin. These findings underscore the complexity of the genetic architecture of Mendelian disease in admixed American populations, with both consanguinity and admixture contributing to the risk of autosomal recessive OCA in Colombia.https://doi.org/10.1371/journal.pone.0313777 |
| spellingShingle | Wilmer A Cárdenas Andrew B Conley Shashwat Deepali Nagar Diana L Núñez-Ríos I King Jordan María Claudia Lattig Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia. PLoS ONE |
| title | Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia. |
| title_full | Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia. |
| title_fullStr | Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia. |
| title_full_unstemmed | Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia. |
| title_short | Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia. |
| title_sort | ancestral origins of tyr and oca2 gene mutations in oculocutaneous albinism from two admixed populations in colombia |
| url | https://doi.org/10.1371/journal.pone.0313777 |
| work_keys_str_mv | AT wilmeracardenas ancestraloriginsoftyrandoca2genemutationsinoculocutaneousalbinismfromtwoadmixedpopulationsincolombia AT andrewbconley ancestraloriginsoftyrandoca2genemutationsinoculocutaneousalbinismfromtwoadmixedpopulationsincolombia AT shashwatdeepalinagar ancestraloriginsoftyrandoca2genemutationsinoculocutaneousalbinismfromtwoadmixedpopulationsincolombia AT dianalnunezrios ancestraloriginsoftyrandoca2genemutationsinoculocutaneousalbinismfromtwoadmixedpopulationsincolombia AT ikingjordan ancestraloriginsoftyrandoca2genemutationsinoculocutaneousalbinismfromtwoadmixedpopulationsincolombia AT mariaclaudialattig ancestraloriginsoftyrandoca2genemutationsinoculocutaneousalbinismfromtwoadmixedpopulationsincolombia |