Demographic history and biologically relevant genetic variation of Native Mexicans inferred from whole-genome sequencing

Romero‐Hidalgo, Sandra; Ochoa-Leyva, Adrián; Garcíarrubio, Alejandro; Acuña-Alonzo, Víctor; Antúnez-Argüelles, Erika; Balcazar-Quintero, Martha; Barquera, Rodrigo; Carnevale, Alessandra; Cornejo‐Granados, Fernanda; Fernández-López, Juan Carlos; García-Herrera, Rodrigo; Garcia‐Ortíz, Humberto; Granados-Silvestre, Ángeles; Granados, Julio; Guerrero‐Romero, Fernando; Hernández‐Lemus, Enrique; León-Mimila, Paola; Macín-Pérez, Gastón; Martínez‐Hernández, Angélica; Márta, Mészáros; Morett, Enrique; Orozco, Lorena; Ortíz-López, Guadalupe; Pérez-Villatoro, Fernando; Rivera‐Morales, Javier; Riveros-Mckay, Fernando; Villalobos-Comparán, Marisela; Villamil‐Ramírez, Hugo; Villarreal-Molina, Teresa; Canizales‐Quinteros, Samuel; Soberón, Xavier

doi:10.1038/s41467-017-01194-z

Cited by 44 publications

(49 citation statements)

References 65 publications

(77 reference statements)

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“…Ruben Lisker performed the first works of Mexican genetics in indigenous populations in the 1960s [ 9 , 22 ], in which he tried to know the degree of admixture as well as the main ancestral components present in these populations. Recently, some studies have been carried out at the molecular level with the aim of knowing the underlying relationships between indigenous and mestizos [ 19 – 21 ], to reconstruct the history of the Amerindian populations in the continent [ 50 ] and their development throughout the country [ 21 ]. Additionally, these works have explored the possible effects of the genetic content in the clinic context [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…There are few works about population genetics in Mexico [ 19 – 21 ]. The first studies were performed by Lisker and colleagues, in indigenous and mestizo populations by studying several blood antigens [ 9 , 22 ]; however, few populations were studied and currently there is lack of information about blood groups distribution in the country, whereby it is essential to get this information to help health institutions for the effective management of their blood banks that facilitate transplant medicine practices.…”

Section: Introductionmentioning

confidence: 99%

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Blood Groups Distribution and Gene Diversity of the ABO and Rh (D)Lociin the Mexican Population

Canizalez-Román

Campos‐Romero²,

Castro-Sánchez³

et al. 2018

BioMed Research International

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Objective To determine the frequency and distribution of ABO and Rh (D) antigens and, additionally, investigate gene diversity and the structure of Mexican populations. Materials and Methods Blood groups were tested in 271,164 subjects from 2014 to 2016. The ABO blood group was determined by agglutination using the antibodies anti-A, Anti-B, and Anti-D for the Rh factor, respectively. Results The overall distribution of ABO and Rh (D) groups in the population studied was as follows: O: 61.82%; A: 27.44%; B: 8.93%; and AB: 1.81%. For the Rh group, 95.58% of people were Rh (D), and 4.42% were Rh (d). Different distributions of blood groups across regions were found; additionally, genetic analysis revealed that the IO and ID allele showed an increasing trend from the north to the center, while the IA and Id allele tended to increase from the center to the north. Also, we found more gene diversity in both loci in the north compared with the center, suggesting population structure in Mexico. Conclusion This work could help health institutions to identify where they can obtain blood products necessary for medical interventions. Moreover, this piece of information contributes to the knowledge of the genetic structure of the Mexican populations which could have significant implications in different fields of biomedicine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blood Groups Distribution and Gene Diversity of the ABO and Rh (D)Lociin the Mexican Population

Canizalez-Román

Campos‐Romero²,

Castro-Sánchez³

et al. 2018

BioMed Research International

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“…(ran on 28/06/17) To test for enrichment in GO categories among genes with novel missense SNV we used WebGestalt online tool(J. Wang et al 2013) as reported in (Romero-Hidalgo et al 2017a).…”

Section: Formentioning

confidence: 99%

Population history and gene divergence in Native Mexicans inferred from 76 human exomes

Ávila‐Arcos

McManus

Sandoval

et al. 2019

Preprint

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Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico's indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 kya and subsequently diverging locally 6.5 kya and 5.7 kya, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern indigenous group from Oaxaca whose height is extremely low compared to other native populations.

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“…A second limitation is enrollment of Mexican population from the same city, not having a random sample from overall Mexican population. However, considering the ethnical background of Mexicans in general, it is not expected to have a great variation of phenotypes since the habitants ancestry is fairly homogeneous [27]. Thirdly, due to ethical reasons, the trials included in this study were executed following a single dose/concentration schedule, in order to reduce the unnecessary risk of possible harm, especially since the active ingredients are known compounds and their posology has already been stablished.…”

Section: Discussionmentioning

confidence: 99%

Reexamining Ophthalmic Drugs, Safety and Tolerability in Phase 1 Clinical Trials

Muñoz‐Villegas

Navarro-Sánchez

Sánchez‐Ríos

et al. 2020

Preprint

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Background: The purpose of this study was to evaluate the safety and tolerability profile of drugs used for treating common eye disorders when applied to normal healthy volunteers (NHV) as explored in phase 1 trials. Methods: A total of 166 NHV were identified in six phase 1 trials. These included the exposure to lubricant (n=88), hypotensive (n=48) or antibiotic (n=30) ophthalmic drugs, examined in a retrospective analysis. The primary endpoints were visual comfort, assessed by the ocular comfort index (OCI); and safety, evaluated through laboratory evaluations, vital signs, visual acuity (VA), intraocular pressure (IOP), lissamine green and fluorescein staining, conjunctival hyperemia, chemosis, and the incidence of adverse events (AE). Other measured parameters included discomfort (assessed by burning, itching and foreign body sensation) and conjunctival impression cytology. Results: Compared to baseline, 72.3%, 39.6% and 66.7% of participants (for lubricant, hypotensive and antibiotic treatments, respectively), improved their OCI score by their final visit (p=0.001). As expected for NHV, laboratory evaluations and vital signs were within normal ranges in 88% of NHV, with no significant differences observed between treatments. Similar results were found for VA, corneal and conjunctival staining and chemosis. IOP decreased significantly in the hypotensive agents group (p=0.001), trace to mild hyperemia was reported in 20.7%, 26% and 5.2% of NHV in each group (p=0.006). Additionally, lubricant and hypotensive investigational drugs (ID) had a lower risk of incidence of AE than approved drugs (AD) of these groups (OR 0.856, 95% CI [0.365, 1.999], and OR 0.636, 95% CI [0.096, 4.195], respectively). Meanwhile, on antibiotic drugs the risk for ID related AE was higher (OR 1.313, 95% CI [0.309, 5.583]). Conclusions: Phase 1 trials are important in order to ensure the safety and tolerability of ophthalmic medications. This study demonstrates that NHV do not face a significant risk of harm in these studies, since 98% of the reported AE were mild, and all AE were resolved by the end of the study in which they appeared. Furthermore, it was also demonstrated that the instillation of ID is as safe and tolerable as that of AD in NHV.Trial registration: The studies were registered at clinicaltrials.gov as follows: NCT04081610, NCT03524157, NCT03520348, NCT03966365, NCT03965052 and, NCT03519516.

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Demographic history and biologically relevant genetic variation of Native Mexicans inferred from whole-genome sequencing

Cited by 44 publications

References 65 publications

Blood Groups Distribution and Gene Diversity of the ABO and Rh (D)Lociin the Mexican Population

Blood Groups Distribution and Gene Diversity of the ABO and Rh (D)Lociin the Mexican Population

Population history and gene divergence in Native Mexicans inferred from 76 human exomes

Reexamining Ophthalmic Drugs, Safety and Tolerability in Phase 1 Clinical Trials

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