Mexican Ancestry Research Articles

The Blueprint for Dred Scott: United States v. Dow and the Multi-Racial Jurisprudence of White Supremacy

Chief Justice Taney’s 1857 opinion in Dred Scott v. Sandford is justly infamous for its holdings that African Americans could never be citizens, that Congress was powerless to prohibit slavery in the territories, and for its proclamation that persons of African ancestry “had no rights which the white man was bound to respect.” For all of the interest in and attention to Dred Scott, however, no scholar has previously analyzed United States v. Dow, an 1840 decision of Chief Justice Taney in a Circuit Court trial which is apparently the first federal decision to articulate a broad theoretical basis for White supremacy. Dow identified Whites as the “master” race, and it explained that only those of European origin were either welcomed or allowed to be members of the political community in the colonies. Non-Whites such as members of Dow’s race, Taney explained, could be reduced to slavery, and therefore their rights continued to be subject to absolute legislative discretion. Dow, however, was not a person of African descent, he was Malay, from the Philippines. Chief Justice Taney’s employment in Dow of legal reasoning which he would later apply in Dred Scott suggests that Dred Scott should be regarded as pertinent to all people of color, not only African Americans. This understanding of Dred Scott helps explain the revival of Taney’s reputation during the Jim Crow era after Reconstruction. Courts declined to invalidate restrictions with respect to a broad range of civil rights on citizens and immigrants of African, Indian, Asian, and Mexican ancestry to which Whites were not subject. Indeed, Whites could not be subject to them, unless it is conceivable that under the U.S. Constitution, the law could provide, for example, that all races would be ineligible to testify or vote because of their race. Accordingly, even after Reconstruction, just as Dred Scott and Dow contemplated, the White race remained the master race, in the sense that they were the exclusive holder of truly inalienable rights.

Screening of IRF6 Variants in Patients Subjected to Genetic Association Studies for Nonsyndromic Cleft Lip/Palate

To screen for interferon regulatory factor 6 (IRF6) pathogenic variants in patients clinically diagnosed with nonsyndromic cleft lip palate (NSCL/P) and establish the proportion of misdiagnosed Van der Woude syndrome (VWS) cases, which could have biased previous NSCL/P case-control association studies. Retrospective case series. Tertiary care children's hospital. One hundred seventy-two unrelated Mexican patients with NSCL/P, 128 of whom had previously been included in a NSCL/P case-control association study. Sanger sequencing of the 9 IRF6 exons were performed, all variants respect with sequence reference were reported and classified for their pathogenic significance according to the American College of Medical Genetics and Genomics guidelines. Seven percent of cases were familial. No pathogenic variant was identified in IRF6. We identified 12 previously reported benign variants; their frequencies did not significantly differ from those reported for individuals of Mexican ancestry. Three of them were uncommon intronic variants not reported in ClinVar. The rs2235371 and rs2235375 variants, which were previously analyzed in a NSCL/P case-control association study (containing 132 patients, 128 of whom were analyzed herein) did not show discordant association results comparing to the 370 controls from the previous study. The misdiagnosis of IRF6-related VWS as NSCL/P appears to be infrequent in our sample, suggesting that mutational screening of IRF6 would have a low diagnostic yield in patients with NSCL/P. The absence of IRF6 pathogenic alleles could be related to the application of an exhaustive clinical evaluation that discarded the syndromic forms and/or the low proportion of familial cases included.

Population-specific genetic background for the OPRM1 variant rs1799971 (118A>G): implications for genomic medicine and functional analysis.

The mu-opioid receptor (MOR, OPRM1) has important roles in diverse functions including reward, addiction, and response to pain treatment. SNP rs1799971 (118A > G, N40D) which occur at a high frequency (40-60%) in Asia and moderate frequency (15%) in samples of European ancestry, is the only common coding variant in the canonical transcript, in non-African populations. Despite extensive studies, the molecular consequences of this variation remained unresolved. The aim of this study was to determine the genetic background of the OPRM1 region of 118G in four representative populations and to assess its potential modulatory effect. Seven common haplotypes with distinct population distribution were identified based on seven SNPs. Three haplotypes carry the 118G and additional highly linked regulatory SNPs (e.g., rs9383689) that could modulate the effect of 118G. Extended analysis in the 1000 Genomes database (n = 2504) revealed a common East Asian-specific haplotype with a different genetic background in which there are no variant alleles for an upstream LD block tagged by the eQTL rs9397171. The major European haplotype specifically includes the eQTL intronic SNP rs62436463 that must have arisen after the split between European and Asian populations. Differentiating between the effect of 118G and these SNPs requires specific experimental approaches. The analysis also revealed a significant increase in two 118A haplotypes with eQTL SNPs associated with drug addiction (rs510769) and obesity (rs9478496) in populations with native Mexican ancestry. Future studies are required to assess the clinical implication of these findings.

Correlation between genetic variation in thymine DNA glycosylase and smoking behavior

Cigarette smoking is a major lifestyle factor leading to different human diseases. The DNA repair gene, thymine DNA glycosylase, is important to cell survival because it stops cells from becoming cancerous protecting/preventing DNA. Exposure to CS may induce genetic changes such as single nucleotide polymorphisms in DNA repair genes. Therefore, the purpose of this study was to investigate the genotype and allele distributions of four TDG SNPs with only smoking behavior in normal patients. Four TDG SNPs—rs4135066 (C/T), rs3751209 (A/G), rs1866074 (C/T), and rs1882018 (C/T) were analyzed by genotyping 235 and 239 blood samples collected from cigarette smokers and non-smokers, among the Saudi population. The results showed that TDG rs4135066 has a significant susceptibility effect observed in long-term smokers (>5 years; OR = 4.53; P = 0.0347) but not in short-term smokers (≤5 years) in contrast with non-smokers. Also, in smokers aged less than 29 years, the “CT,” “TT,” and “CT + TT” alleles of rs1882018 increased the risk of developing all diseases related to smoking by approximately 6, 4, and 5 times, respectively, in contrast with the ancestral “CC” homozygous allele. A comparison of the allele distributions of TDG SNPs in a Saudi population with those in other populations represented in the HapMap project showed that the genetic makeup of the Saudi Arabian population appears to differ from that of other ethnicities. Exceptions include the Yoruba people in Ibadan, Nigeria; those of Mexican ancestry in Los Angeles, California; the Luhya population in Webuye, Kenya; Gujarati Indians in Houston, Texas; and the Tuscan population in Italy, which showed similar allelic frequencies for rs3751209 compared to our Saudi population. In this ethnic, we have found a high variation in the distribution of the alleles and genotype frequencies on TDG gene. This variation on TDG SNP’s with smoking could lead to increase the susceptibility to many diseases related to smoking habits in this population.

Genetic Analysis of Pharmacogenomic VIP Variants of ABCB1, VDR and TPMT Genes in an Ethnically Isolated Population from the North Caucasus Living in Jordan.

Differences in individual responses to the same medications remarkably differ among populations. A number of genes that play integral roles in drug responses have been designated as very important pharmacogenes (VIP), as they are responsible for differences in drug safety, efficacy, and adverse drug reactions among certain ethnic groups. Identifying the polymorphic distribution of VIP in a range of ethnic groups will be conducive to population-based personalized medicine. The aim of the current study is to identify the polymorphic distribution of VIP regarding the Chechen minority group from Jordan and compare their allele frequencies with other populations. A total of 131 unrelated Chechen individuals from Jordan were randomly recruited for blood collection. Identification of allelic and genotypic frequencies of eleven VIP variants within the genes of interest (ABCB1, VDR and TPMT) was carried out by means of the MassARRAY®System (iPLEX GOLD). Within ABCB1, we found that the minor allele frequencies of the rs1128503 (A: 0.43), rs2032582 (A: 0.43), rs1045642 (A: 0.43). For VDR, the minor allele frequencies of rs11568820 (T: 0.18), rs1540339 (T: 0.30), rs1544410 (T: 0.41), rs2228570 (T: 0.24), rs3782905 (C: 0.28) and rs7975232 (C: 0.45). Finally, the minor allele frequencies for the TPMT rs1142345 and rs1800460 polymorphisms were found to be (C: 0.02) and (T: 0.01), respectively. Significant differences in allelic frequencies of eleven ABCB1, VDR and TPMT VIP variants were found between Jordanian Chechens and other populations. In our study, most populations that are similar to Chechens are those from South Asian, European (Finnish) and European, including: Utah residents with Northern and Western European ancestry, Toscani in Italia, Mexican ancestry in Los Angeles and Circassian from Jordan. The level of similarity between Chechens and those populations means that they might have shared high levels of gene flow in the past. The results obtained in this study will contribute to the worldwide pharmacogenomic databases and provide valuable information for future studies and better individualized treatments.

Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma.

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Abstract C045: Polymorphism in CYP1B1 increases CRC risk in Puerto Rican individuals that consume processed meats

Abstract Colorectal cancer (CRC) is the 1st cause of cancer-related deaths in Puerto Rico (PR). CRC is a heterogeneous disease with lifestyle and environmental factors shown to modify the risk to develop this disease. High intake of red and processed meats was determined to be a risk factor for increased risk of CRC. Genetic variations in genes involved in the metabolism of meat carcinogens have been found to be associated with CRC risk and to vary across racial/ethnic populations. The objective of this project was to determine the association of functional genetic variants in meat-carcinogen metabolism genes with CRC risk in the PR population. First, we analyzed the allelic frequencies of SNPs in key meat carcinogen metabolism genes (CYP1A1, CYP1B1, NAT2 and CYP2E1), that were previously reported to have an association with development of colorectal adenomas or CRC were evaluated in the 1000 Genomes Populations. The 1000 Genomes populations included AFR (African Populations), EUR (European Populations), CLM (Colombians from Medellin, Colombia), MXL (Mexican Ancestry from Los Angeles USA), PEL (Peruvians from Lima Peru) and PUR (Puerto Ricans from Puerto Rico). Then, we genotyped using TaqMan technology 5 functional SNPs localized at key meat carcinogen detoxifying genes, CYP1A1, CYP1B1, NAT1, NAT2 and CYP2E1 in Puerto Ricans (205 CRC cases and 218 controls). Our preliminary results showed that the allelic frequencies of the SNPs differ between PUR and the other 1000 Genomes populations, suggesting that these SNPs might have a distinct effect on the association of red/processed meat intake and CRC risk on Puerto Ricans. Furthermore, genotyping analysis showed that individuals with the AA genotype at the rs1800440 SNP (CYP1B1) who consume processed meat 2-4 times per week were at increased risk of CRC (p=0.008). These preliminary data support a role for genetic variants in genes that play key roles in the mechanisms of meat carcinogenesis as possible modifiers of the carcinogenic effects of meat. Citation Format: Julyann Perez-Mayoral, Maria E. Perez-Hernandez, Mariana Stern, Marcia R. Cruz-Correa. Polymorphism in CYP1B1 increases CRC risk in Puerto Rican individuals that consume processed meats [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C045.

The CFTR variant profile of Hispanic patients with cystic fibrosis: Impact on access to effective screening, diagnosis, and personalized medicine.

Hispanic patients comprise an appreciable and increasing proportion of patients with cystic fibrosis (CF) in the United States (US). Hispanic patients with CF are known to have increased morbidity and mortality compared to non-Hispanic white patients with CF, and ongoing investigations are underway to identify contributing factors amenable to intervention in order to address the disparate health outcomes. One contributing factor is the different CF transmembrane conductance regulator (CFTR) variant profile observed in Hispanic patients with CF. The most common CFTR variant, p.Phe508del (legacy name F508del), is proportionally underrepresented in Hispanic patients with CF. This difference has implications for prenatal screening, newborn screening (NBS), and CFTR variant-specific therapeutic options. In particular, the recent approval of a highly effective CFTR modulator for patients carrying at least one copy of F508del, elexacaftor/tezacaftor/ivacaftor triple combination therapy, underscores the potential for unequal access to personalized treatment for Hispanic patients with CF. We report the CFTR variant profiles of Hispanic patients with CF and non-CF Hispanic infants with a false-positive New York State CF NBS at a single center in New York City over a 5-year study period, as an opportunity to address the racial and ethnic disparities that currently exist in CF screening, diagnosis, and treatment. In addition to the previously documented disparate prevalence of the CFTR variant F508del in Hispanic patients, we observed two CFTR variants, p.His609Arg (legacy name H609R) and p.Thr1036Asn (legacy name T1036N), frequently identified in our Hispanic patients of Ecuadorian and Mexican ancestry, respectively, that are not well-described in the US population. The presence of population-specific and individually rare CFTR variants in Hispanic patients with CF further accentuates the disparity in health outcomes, as these CFTR variants are often absent from prenatal and NBS CFTR variant panels, potentially delaying diagnosis, and without an approved CFTR variant-specific therapy.

FUT2 polymorphism in Latin American populations

BackgroundThe secretor type α(1,2)fucosyltransferase gene (FUT2) is known to be rich in population-specific polymorphisms. However, genetic variations of FUT2 have not been well examined in Latin American populations in which nonsecretors are rare. MethodsConventional polymerase chain reactions and direct sequencing were performed to detect single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) of FUT2 in Mexicans including Americans of Mexican ancestry, Puerto Ricans, Caribbeans, and Colombians. FUT2 alleles were determined by cloning into plasmids or PHASE software. The impact of uncharacterized missense SNPs on the enzyme activity were examined by transient transfection assays and estimated by several software programs. ResultsThree alleles, Se357, Se, and se428, were common, and the frequency of nonsecretors was relatively low in the studied populations. We also encountered several alleles specific to Africans, Europeans, and South and East Asians including a South Asian-specific sedel. In contrast to the in silico prediction, a transient expression study suggested that both of two missense SNPs, 235G > A and 304G > A, did not impair the enzyme activity. ConclusionsThe allelic polymorphism of FUT2 suggests that the modern Latin American populations were formed via genetic admixture among Native Americans and populations whose ancestors migrated from other continents. In this study, we have observed a discrepancy between in silico and functional analyses for FUT2 for the first time. Therefore, experimental functional analysis is required for evaluation of SNPs of FUT2.

EXPLORATORY ANALYSIS OF POLYGENIC RISK SCORES FOR PSYCHIATRIC DISORDERS: APPLIED TO DUAL DIAGNOSIS.

Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

Elucidating the Multidimensionality of Socioeconomic Status in Relation to Metabolic Syndrome in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Socioeconomic (SES) factors underlying disparities in the prevalence of metabolic syndrome (MetSyn) and consequently, type 2 diabetes among Hispanics/Latino populations are of considerable clinical and public health interest. However, incomplete and/or imprecise measurement of the multidimensional SES construct has impeded a full understanding of how SES contributes to disparities in metabolic disease. Consequently, a latent-variable model of the SES-MetSyn association was investigated and compared with the more typical proxy-variable model. A community-based cross-sectional probability sample (2008-2011) of 14,029 Hispanic/Latino individuals of Puerto Rican, Cuban, Dominican, Central American, South American, and Mexican ancestry living in the USA was used. SES proxy's education, income, and employment were examined as effect indicators of a latent variable, and as individual predictors. MetSyn was defined using 2009 harmonized guidelines, and MetSyn components were also examined individually. In multivariate regression analyses, the SES latent variable was associated with 9% decreased odds of MetSyn (95% confidence interval: 0.85, 0.96, P < .001) and was associated with all MetSyn components, except diastolic blood pressure. Additionally, greater income, education, and employment status were associated with 4%, 3%, and 24% decreased odds of having MetSyn, respectively (Ps < .001). The income-MetSyn association was only significant for women and those with current health insurance. Hispanic/Latinos exhibit an inverse association between SES and MetSyn of varying magnitudes across SES variables. Public health research is needed to further probe these relationships, particularly among Hispanic/Latina women, to ultimately improve healthcare access to prevent diabetes in this underserved population.

Trump’s Latinx Repatriation

Two historical episodes have indelibly influenced the development of Latinx identity and sense of belonging in the United States. During the Great Depression, state and local governments, with the support of the U.S. government, repatriated approximately one million persons of Mexican ancestry, including many U.S. citizen children as well as immigrant parents, to Mexico. Similarly, in 1954, the U.S. government launched Operation Wetback, a military-style campaign led by a retired general that removed another one million persons of Mexican ancestry, including many U.S. citizen children, from the Southwest. History rightly condemns these episodes of anti-Mexican intolerance, which amount to an ethnic cleansing. Nonetheless, we may be seeing history repeat itself with even greater harm inflicted on larger numbers of Latinx peoples. Through breathtaking and unprecedented changes to immigration enforcement, President Donald J. Trump has boldly moved to reduce immigration to, and the number of immigrants in, the United States. This Article contends that, as part and parcel of his fervent anti-immigrant agenda, President Trump is engaging in a concerted effort to remove Latinx people, especially Mexicans and Central Americans, from the country. Just as the previous Mexican removal campaigns did, the new Latinx repatriation accomplishes mass removals and encourages Latinx noncitizens, along with U.S. citizen children, to leave the country and self-deport, or, alternatively, to never come to the United States in the first place. But the new Latinx repatriation differs in important respects from the old removal campaigns. First, the new system is facially-neutral and colorblind, not expressly targeting Latinx people. That is the case even though President Trump’s words frequently—and mercilessly—attack Latinx immigrants. Second, through President Trump’s policy efforts, the new repatriation has become institutionalized into the ordinary operation of immigration enforcement, which differs from the ad hoc and episodic nature of the Mexican repatriation and Operation Wetback. With the targeting of Latinx immigrants embedded in the institutional structure of immigration enforcement, one can expect many more Latinx noncitizens to be removed than in previous Mexican removal campaigns. Ultimately, meaningful change to the racial discrimination embedded in immigration law and its enforcement only can be addressed through political action and congressional reform of the immigration laws. To do so, we must acknowledge and address head-on the racial impacts of the operation of the immigration laws and their enforcement. Put differently, an awareness of the racialized nature of the problem is a precursor to bringing racial justice to immigration.

The New Latinx 'Repatriation'? Removals, Criminal Justice, and the Efforts to Remove Latinx Peoples from the United States

Several historical episodes have indelibly influenced the sense of belonging of generations of persons of Mexican ancestry - and Latinx generally - in the United States. Two powerful examples aptly illustrate this point. During the hard times of the Great Depression, state and local governments, with the support of the U.S. government, “repatriated” approximately one million persons of Mexican ancestry, including many U.S. citizen children as well as immigrant parents, to Mexico. Similarly, the U.S. government in 1954 in the military-style “Operation Wetback,” directed by a retired general, removed hundreds of thousands of persons of Mexican ancestry, including many U.S. citizen children, from the Southwest. Those discriminatory events have shaped the identities of Latinx people in the United States. History has condemned these episodes of racial intolerance. Nonetheless, we may be seeing history repeat itself, but with even larger numbers of people injured. Ushering in breath-taking changes in immigration law and enforcement, President Donald J. Trump has boldly moved to reduce immigration to, and the number of immigrants in, the United States. This Article contends that, because so many of the measures directly and indirectly target Latina/os, they represent the equivalent of an attempt at a “new” Mexican repatriation– a concerted effort to remove Latinx people, focusing on Mexicans and Central Americans, from the country. Just as the previous campaigns did, the new efforts further encourage Latinx non-citizens, along with U.S. citizen children, to “self-deport” (i.e., leave the country) or to never come to the United States. Part I of this Article reviews previous efforts to remove persons of Mexican ancestry from the United States, namely what is known as the “Mexican repatriation” during the Great Depression and “Operation Wetback” in 1954. Part II considers the impacts on Latinx of the contemporary efforts by the Trump administration to remove immigrants from the United States, and to reduce legal immigration. It further draws parallels between the “new” and “old” repatriation campaigns.

Identification of novel hyper-or hypomethylated CpG sites and genes associated with atherosclerotic plaque using an epigenome-wide association study.

DNA methylation is an important epigenetic modification that has been implicated in the pathogenesis of atherosclerosis. Although previous studies have identified various CpG sites and genes whose methylation is associated with atherosclerosis in populations with European or Mexican ancestry, the genome-wide pattern of DNA methylation in the atherosclerotic human aorta is yet to be elucidated in Japanese individuals. In the present study, a genome-wide analysis of DNA methylation at ~853,000 CpG sites was performed using 128 postmortem aortic intima specimens obtained from 64 Japanese patients. To avoid the effects of interindividual variation, intraindividual paired comparisons were performed between atheromatous plaque lesions and corresponding plaque-free tissue for each patient. Bisulfite-modified genomic DNA was analyzed using a specific microarray for DNA methylation. DNA methylation at each CpG site was calculated as the β value, where β = (intensity of the methylated allele)/(intensity of the methylated allele + intensity of the unmethylated allele + 100). Bonferroni's correction for statistical significance of association was applied to compensate for multiple comparisons. The methylation of 2,679 CpG sites differed significantly (P<5.86×10−8) between atheromatous plaque lesions and the corresponding plaque-free intima, with 2,272 and 407 CpG sites in atheromatous plaques being hyper- or hypomethylated, respectively. A total of 5 hypermethylated CpG sites in atheromatous plaques were demonstrated to have a difference in β value of >0.15 (plaque lesion-plaque-free intima) and 11 had a β ratio of >1.50 (plaque/plaque-free intima). A further 15 and 17 hypomethylated CpG sites in atheromatous plaques were observed to have a difference in β value of <−0.15 or a β ratio of <0.67, respectively. According to these limits, a total of 16 novel genes that were significantly hyper- or hypomethylated in atheromatous plaque lesions compared with the plaque-free intima were identified in the present study. The results of the present study suggest that the methylation of these genes may contribute to the pathogenesis of atherosclerosis in the Japanese population.

Houston Bound: Culture and Color in a Jim Crow City by Tyina L. Steptoe

Reviewed by: Houston Bound: Culture and Color in a Jim Crow City by Tyina L. Steptoe Bernadette Pruitt Houston Bound: Culture and Color in a Jim Crow City. By Tyina L. Steptoe. (Oakland: University of California Press, 2016. Pp. 327. Illustrations, notes, bibliography, index.) The experiences of ancestors often influence the work of professional historians, providing them with the intellectual tools necessary to understand self, family, community, and the world. Following this tradition, University [End Page 463] of Arizona scholar and Houston native Tyina L. Steptoe's masterful work, Houston Bound: Culture and Color in a Jim Crow City, honors, among others, her ancestors—Creoles of color—whose determination, work ethic, cultural ingenuity, and activism made her success possible. A culturalpolitical history, Houston Bound examines four ethnic communities: African Americans from East Texas; African-descent Creoles from Southwest Louisiana; Tejanos from Central and South Texas; and Mexican nationals fleeing Revolutionary Mexico. Ultimately, the newcomers' cultural tenets helped ferment varied civil rights movements at a time when whites were imposing systems of segregation based on a black/white dichotomy. With the use of an impressive array of records and sources, including manuscript collections, War Department materials, oral histories, music, newspapers, government documents such as census data and vital statistics, and secondary sources, written in English, Spanish, and French, the author reconstructs the complex, interwoven histories of these four groups of Houstonians whose appearance during the Great Migrations (the mass, overlapping movements of an estimated two hundred thousand culturally varied people within and into the United States between 1900 and 1950) helped shape the historical contours of what would ultimately become the nation's fourth largest city. Not surprisingly, the history of these groups in Houston correlates with their experiences as both the displaced poor and as people perceived as inferior by the white majority culture. Racialized segregation, job inequality, inadequate public schooling, disfranchisement, and violence all fostered discrimination and caused irreparable harm in rural communities and small towns in East Texas and Southwest Louisiana. So too did natural disasters inflict misery. The devastating Great Mississippi Flood of 1927 precipitated the migrations of tens of thousands of African-descent Louisianans into Texas. Descendants of multiracial parentage, they defined themselves as Creoles or Creoles of color, believing the cultural and phenotypical differences that separated them from most black people also distinguished them as proudly and historically special. Racism and poverty also affected Tejanos—Texans of Spanish and Amerindian origin—whose lives intersected with black newcomers. Tejanos were oppressed even in South and West Texas, where they outnumbered whites. In Mexico, socioeconomic instability caused by the 1910 Revolution caused mass exoduses to the north, with 1.5 million people relocating permanently to the United States, including several thousand to Houston. The Great Migrations brought into the city tens of thousands of Latinos, ushering in a fascinating cultural renaissance: a social admixture of folk music, the arts, and political satire that took place from the 1900s to the 1960s. In the early decades, Creole music and East Texas blues helped usher in jazz, a sound influenced by urbanization and industrial [End Page 464] growth. Two Latino sounds also emerged in the 1900s and 1910s: corridos and conjunto among Tejanos and boleros and ranchera among Mexican nationals. The city's growing economy stimulated new migration streams in the 1920s. Politically, "New Negro" and Mexican American generations emerged with divergent voices, creating their own respective protest initiatives to dismantle segregation and racial bigotry. These groups, their children, and other early twentieth-century newcomers, however, eventually precipitated pathways for inclusivity. From the 1920s through the 1940s, the growth of swing music and the plethora of jazz clubs that opened throughout Houston confirmed the successful collaborations of New Negroes and their ability to earn decent livings. For Latinos, Mexican-oriented big bands called orquestas attracted New Negroes, especially from elite families. In the 1950s and 1960s, Latinos, Creoles, and African Americans crossed musical lines of demarcation through the rise of rhythm and blues and soul music. At the same time, younger Hispanics of Mexican ancestry now embraced their indigenous roots, calling themselves Chicanos. Rejecting the older civil-rights strategy of LULAC president Felix Tijerina, they built on the Black...

Characterization of Large Copy Number Variation in Mexican Type 2 Diabetes subjects

The effect of Copy Number Variants (CNVs) on Type 2 Diabetes (T2D) remains little explored. The present study characterized large rare CNVs in 686 T2D and 194 non-T2D subjects of Mexican ancestry genotyped using the Affymetrix Genome-Wide Human SNP array 5.0. Rare CNVs with ≥ 100 kb length were identified using a stringent strategy based on merging CNVs calls generated using Birdsuit, iPattern and PennCNV algorithms. We applied three different strategies to evaluate the distribution of CNVs in the T2D and non-T2D samples: 1) Burden analysis, 2) Identification of CNVs in loci previously associated to T2D, and 3) Identification of CNVs observed only in the T2D group. In the CNV burden analysis, the T2D group showed a higher proportion of CNVs, and also a higher proportion of CNVs overlapping at least one gene than the non T2D group. Five of the six loci previously associated with T2D had duplications or deletions in the T2D sample, but not the non-T2D sample. A gene-set analysis including genes with CNVs observed only in the T2D group highlighted gene-sets related with sensory perception (olfactory receptors, OR) and phenylpyruvate tautomerase/dopachrome isomerase activity (MIF and DDT genes).

Prevalence and ancestral origin of the c.1987delC GAA gene mutation causing Pompe disease in Central Mexico

Pompe Disease (PD) is a rare autosomal recessive disorder caused by lysosomal enzyme acid-alpha-glucosidase (GAA) deficiency, which leads to lysosomal glycogen accumulation, swelling, cellular damage and dysfunction of cardiac, respiratory and muscular tissue. In Mexico, <100 PD cases have been diagnosed. Recently, three apparently unrelated classic infantile PD cases coming from three different isolated communities of Central Mexico were diagnosed at the same hospital in the State of San Luis Potosi, and were found to be homozygous for a novel frameshift GAA gene mutation (c.1987delC). The purpose of the study was to determine mutation carrier frequencies in these localities, to alert the authorities on the high risk of PD in this region, to gain insight on the structural effects of the mutation by protein modeling, and to disclose the ancestral origin of the mutation. Quantitative PCR analyses showed that 24/307 (7.8%) subjects from two of the communities were heterozygous for the mutation. A genetic counseling campaign and newborn screening were organized with the help of local authorities. Tridimensional modeling predicted the mutant c.1987delC the second of the 3 GAA domains would be improperly folded and the third domain missing. Global ancestry analysis of six individuals from these communities (5 mutation carriers and 1 non-carrier) showed that >95% of their genetic component was of Native Mexican origin, while <4% was of European origin. The GAA mutation was found to lie within a segment of Native Mexican ancestry, probably Mayan-Zapotec.

Subjective well-being among Latino day laborers: Examining the role of religiosity, social networks, and cigarette use.

Background: Latino day laborers (LDLs) experience chronic stressors, that adversely affects their subjective well-being (SWB). The purpose of the study was to determine whether LDLs’ sociodemographic characteristics, religiosity, social networks, and cigarette use were significantly associated with SWB.Methods: AApproximately 150 LDLs from 4 informal day laborer sites in Dallas and Arlington, Texas, participated in the cross-sectional survey. Informed consent was obtained from all participants and data on SWB were collected face-to-face from April 2013 through July 2013.Results: Most respondents were of Mexican ancestry, (n = 112; 75%), were foreign-born (n = 140; 93%), and undocumented (n = 108; 72%). LDLs reported a mean satisfaction with life score of 19.07 (SD=8.52). Thirty percent of LDLs reported not smoking any cigarettes in the past 30 days. However, 20% reported smoking 20–39 cigarettes, while another 20% reported smoking 40 or more cigarettes in the past 30 days. Hierarchical multiple regression results indicated that marital status (β = 0.13, P ≤ 0.05), connectedness to friends (β = 0.21, P ≤ 0.001), the influence of religion on life (β = 0.57, P ≤ 0.01), frequency of attendance to religious institution (β = 0.11, P ≤ 0.005), and cigarette use (β = -0.15, P ≤ 0.05) were significantly associated with the SWB appraisals of LDLs.Conclusion: These findings show that LDLs are resilient and rely on noneconomic factors to enhance their perceived quality of life. The results underscore the need to identify pathways to improve SWB among LDLs. Doing so may address the broader mental health and occupational health disparities gaps that affect LDLs.

Abstract 3414: Novel MGMT variant association in Mexican patients with astrocytoma

Abstract Introduction: Astrocytomas are the most common and lethal brain tumors with a median survival of 15 months. Different biomarkers have arisen to classify and treat this type of tumors; one of these markers is MGMT. The methylation status of this gene is a prognostic and predictive factor. The MGMT (O-6-Methylguanine-DNA Methyltransferase) is involved in the cellular response to the effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. The dysregulation of this methylation is critical in the development of certain cancers. Objective: To identify germinal MGMT gene variations in patients with astrocytoma. Material and methods: 55 randomly selected Mexican patients diagnosed with astrocytoma between 2008-2014 were consented to perform the molecular analysis of the whole gene and 5´UTR and 3´UTR regions of MGMT at Ion Torrent platform. Each amplified region had a depth of minimum 1500x. Ion Reporter software was used to analyze the genetic variants and using Integrative Genomic Viewer we confirmed that each variant had a Phred higher than 25. Genotypic frequencies were compared with HapMapMex and Mexican ancestry population from the 1000 Genomes project. Results. In lymphocytes DNA, eight genetic variants were found, and two of them were statistically significant risk factors: rs7896488 alternative allele A with a frequency of 15% in patients with astrocytoma, and only 4% of the control group (OR=5.53, IC 1.96-15.59 p = 0.0007) and rs2308326 ancestral allele C, where 93% of the patients were carriers of allele C in contrast with 73% of controls (OR=5.39, IC 2.29-12.69 p = 0.000019). These variants are non-coding single nucleotide polymorphisms, rs7896488 is a 3' UTR genetic variant, while rs2308326 is an intronic variant. Conclusion: Our study found two new risk SNV for Astrocytoma in a Mexican population. Citation Format: Liliana Gomez-Flores-Ramos, Talia Wegman-Ostrosky. Novel MGMT variant association in Mexican patients with astrocytoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3414. doi:10.1158/1538-7445.AM2017-3414

A Complete Association of an intronic SNP rs6798742 with Origin of Spinocerebellar Ataxia Type 7-CAG Expansion Loci in the Indian and Mexican Population.

Spinocerebellar ataxia type 7 (SCA7) is a rare neurogenetic disorder caused by highly unstable CAG repeat expansion mutation in coding region of SCA7. We aimed to understand the effect of diverse ATXN7 cis-element in correlation with CAG expansion mutation of SCA7. We initially performed an analysis to identify the haplotype background of CAG expanded alleles using eight bi-allelic single nucleotide polymorphisms (SNPs) flanking an ATXN7-CAG expansion in 32 individuals from nine unrelated Indian SCA7 families and 88 healthy controls. Subsequent validation of the findings was performed in 89 ATXN7-CAG mutation carriers and in 119 unrelated healthy controls of Mexican ancestry. The haplotype analyses showed a shared haplotype background and C allele of SNP rs6798742 (approximately 6 kb from the 3'-end of CAG repeats) is in complete association with expanded, premutation, intermediate, and the majority of large normal (≥12) CAG allele. The C allele (ancestral/chimp allele) association was validated in SCA7 subjects and healthy controls from Mexico, suggesting its substantial association with CAG expanded and expansion-prone chromosomes. Analysis of rs6798742 and other neighboring functional SNPs within 6 kb in experimental datasets (Encyclopedia of DNA Elements; ENCODE) shows functional marks that could affect transcription as well as histone methylation. An allelic association of the CAG region to an intronic SNP in two different ethnic and geographical populations suggests a -cis factor-dependent mechanism in ATXN7 CAG-region expansion.