A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos.

BACKGROUND: Association studies are useful to unravel the genetic basis of common human diseases. However, the presence of undetected population structure can lead to both false positive results and failures to detect genuine associations. Even when most of the approaches to deal with population stratification require genome-wide data, the use of a well-selected panel of ancestry informative markers (AIMs) may appropriately correct for population stratification. Few panels of AIMs have been developed for Latino populations and most contain a high number of markers (> 100 AIMs). For some association studies such as candidate gene approaches, it may be unfeasible to genotype a numerous set of markers to avoid false positive results. In such cases, methods that use fewer AIMs may be appropriate. RESULTS: We validated an accurate and cost-effective panel of AIMs, for use in population stratification correction of association studies and global ancestry estimation in Mexicans, as well as in populations having large proportions of both European and Native American ancestries. Based on genome-wide data from 1953 Mexican individuals, we performed a PCA and SNP weights were calculated to select subsets of unlinked AIMs within percentiles 0.10 and 0.90, ensuring that all chromosomes were represented. Correlations between PC1 calculated using genome-wide data versus each subset of AIMs (16, 32, 48 and 64) were r2 = 0.923, 0.959, 0.972 and 0.978, respectively. When evaluating PCs performance as population stratification adjustment covariates, no correlation was found between P values obtained from uncorrected and genome-wide corrected association analyses (r2 = 0.141), highlighting that population stratification correction is compulsory for association analyses in admixed populations. In contrast, high correlations were found when adjusting for both PC1 and PC2 for either subset of AIMs (r2 > 0.900). After multiple validations, including an independent sample, we selected a minimal panel of 32 AIMs, which are highly informative of the major ancestral components of Mexican mestizos, namely European and Native American ancestries. Finally, the correlation between the global ancestry proportions calculated using genome-wide data and our panel of 32 AIMs was r2 = 0.972. CONCLUSIONS: Our panel of 32 AIMs accurately estimated global ancestry and corrected for population stratification in association studies in Mexican individuals.

Population data for 21 autosomal STR loci (GlobalFiler kit) in two Mexican-Mestizo population from the northwest, Mexico.

Mexican Mestizos (admixed) have been poorly studied for short tandem repeats (STRs) included for new human identification (HID) kits, such as the GlobalFiler PCR Amplification kit. Therefore, this kit was analyzed in 784 unrelated volunteers from the city of Tijuana (n = 381) and Sonora state (n = 403) in the northwest region of Mexico. Allele frequencies, forensic parameters, Hardy-Weinberg equilibrium, and linkage equilibrium were estimated or evaluated for 21 autosomal STRs, respectively. For this HID kit, the combined power of discrimination (PD) was > 0.99999999999999 (RMP range = 1.23 to 3.0 × 10-25), and the combined power of exclusion (PE) were 0.999999993 and 0.999999997 in Tijuana city and Sonora state, respectively. Interpopulation analyses based on STRs of the GlobalFiler kit was performed, including four Mexican Native American, one Mexican Mestizo, and four ethnic American populations (USA), previously studied. The low-but significant-differentiation observed among Mexican Mestizos (FST = 0.0969%; p = 0.02584) justifies the creation of STR databases for HID purposes in this country. In brief, results allow the confident use of the GlobalFiler kit for HID purposes in Mestizo population from the Northwest region Mexico.

IFNG +874 A/T is associated with acute lymphoblastic leukemia in Mexican Mestizos.

Acute lymphoblastic leukemia (ALL), the most common type of cancer in children worldwide, has one of the highest incidence rates in Mexico. It is a multifactorial disease and different cytokine single nucleotide polymorphisms (SNP), have been associated with ALL expression. Few studies have been published analyzing IFNG +874 T/A and IL2 -330 G/T in this type of leukemia. These SNPs are involved in high or low expression, and are central to cellular immunity, influencing greatly tumor growth. The purpose of this work was to explore the association of IFNG +874 A/T (rs2430561) and IL2 -330 G/T (rs2069762) SNPs with ALL susceptibility and/or protection in 488 Mexican Mestizos patients, as compared to 950 Mexican Mestizo healthy controls. The results demonstrated that IFNG +874 T allele (pc = 0.00004, OR = 0.673) and the TT genotype (pc = 0.00015, OR = 0.349), protect against ALL expression with no specific gender association; however, the TT homozygote genotype (vs. TA+AA) seems more protective in males (pc = 0.00683). IL2 -330 G/T does not contribute to the development of ALL. In healthy Mexicans, the most common genotypes for IL2 and IFNG, are the low cytokine producers, suggesting that the genetic background in this ethnic group, may be partly responsible for the high incidence of ALL. These results show for the first time in Mexicans, the relevant role that IFNG SNP has in the genetic etiology of ALL. Thus, a large group of patients belonging to different ethnicities will be very helpful to study in order to demonstrate if these SNPs contribute to the genetic etiology of ALL, as shown here in Mexican Mestizos.

Forensic parameters and admixture in seven geographical regions of the Guerrero state (South, Mexico) based on STRs of the Globalfiler® kit.

BACKGROUND: New commercial STR kits have emerged with greater numbers of markers, which allows for obtaining stronger conclusions in forensic casework, which has been poorly studied in Mexico. AIM: To obtain forensic parameters and to analyse the genetic relationships, structure and admixture in seven geographic regions of Guerrero state (South, Mexico) based on the Globalfiler® kit. SUBJECTS AND METHODS: A total of 245 unrelated Mexican individuals from seven regions of the state of Guerrero were analysed with the Globalfiler® kit. Forensic parameters, pairwise comparisons, genetic distances, structure analysis and admixture levels were estimated. RESULTS: Allele frequencies and forensic parameters of 22 STRs were estimated in this Mexican population sample. The combined power of exclusion and power of discrimination values were > 99.9999% and >99.99999999%, respectively. The Native American, European and African ancestries estimated in the Guerrero state population were 70.9%, 25.9% and 3.2%, respectively. CONCLUSION: Forensic validation of the Globalfiler® kit was performed in the Guerrero state population. The geographic isolation level seems to be the principal factor in defining genetic relationships and admixture among the Guerrero sub-populations. Despite the intrinsic limitations of STRs for admixture analysis, these results are very close to previous values based on AIMs and genome-wide SNPs.

Genetic variation of 17 STR loci in a Mexican Mestizo population from Mexico City.

Genetic data from 17 autosomal short tandem repeat (STR) loci found in the Powerplex® ESX 17 System (Promega, Madison, WI, USA) was evaluated in 162 unrelated Mexican Mestizo individuals from Mexico City. Allele frequencies and forensic parameters were estimated for the 17 STRs. All loci analyzed were in Hardy-Weinberg equilibrium in the studied population and showed not any signs of linkage between loci. The combined power of discrimination and the power of exclusion for the 16 aSTRs studied were 1-2.56409·10-19 and 99.999938 %, respectively. Genetic distances reveal a close relationship within different populations of Mexican Mestizos. The obtained data might be useful for population genetics research and for individual identification and paternity testing in forensic science.

Maternal admixture and population structure in Mexican-Mestizos based on mtDNA haplogroups.

The maternal ancestry (mtDNA) has important applications in different research fields, such as evolution, epidemiology, identification, and human population history. This is particularly interesting in Mestizos, which constitute the main population in Mexico (∼93%) resulting from post-Columbian admixture between Spaniards, Amerindians, and African slaves, principally. Consequently, we conducted minisequencing analysis (SNaPshot) of 11 mitochondrial single-nucleotide polymorphisms in 742 Mestizos of 10 populations from different regions in Mexico. The predominant maternal ancestry was Native American (92.9%), including Haplogroups A, B, C, and D (47, 23.7, 15.9, and 6.2%, respectively). Conversely, European and African ancestries were less frequent (5.3 and 1.9%, respectively). The main characteristics of the maternal lineages observed in Mexican-Mestizos comprised the following: 1) contrasting geographic gradient of Haplogroups A and C; 2) increase of European lineages toward the Northwest; 3) low or absent, but homogeneous, African ancestry throughout the Mexican territory; 4) maternal lineages in Mestizos roughly represent the genetic makeup of the surrounding Amerindian groups, particularly toward the Southeast, but not in the North and West; 5) continuity over time of the geographic distribution of Amerindian lineages in Mayas; and 6) low but significant maternal population structure (FST = 2.8%; P = 0.0000). The average ancestry obtained from uniparental systems (mtDNA and Y-chromosome) in Mexican-Mestizos was correlated with previous ancestry estimates based on autosomal systems (genome-wide single-nucleotide polymorphisms and short tandem repeats). Finally, the comparison of paternal and maternal lineages provided additional information concerning the gender bias admixture, mating patterns, and population structure in Mestizos throughout the Mexican territory.

Mayan alleles of the HLA-DRB1 major histocompatibility complex might contribute to the genetic susceptibility to systemic lupus erythematosus in Mexican patients from Tapachula, Chiapas.

INTRODUCTION: Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease that disrupts numerous immunity mechanisms with the potential to exert damage to any organ or tissue. Its etiology remains uncertain; however, genetic and environmental factors that differ between populations strongly influence its development. Among the physiopathogenic factors, the genetic ones predominate, notably the major histocompatibility complex (MHC) loci. A high degree of ethnical admixture makes Mexican Mestizos a thoroughly genetically heterogeneous population. Therefore, this study aimed to identify the MHC polymorphisms associated with SLE development in Mexican Mestizos from Southern Mexico and compare them with patients from Mexico City. METHOD: A transversal study in SLE patients from Tapachula, Chiapas, was conducted. DNA typing of human leukocyte antigens (HLA) classes I and II was performed using single specific primers (SSP). Admixture analysis was performed using the population genetics LEADMIX software. RESULTS: The frequencies of HLA-DRB1*16 and HLA-DQB1*05 were found to have a tendency towards increase in SLE patients, compared to ethnically matched healthy controls. The allele HLA-DRB1*03 seemed to be less associated with SLE in this group of Mexican Mestizos, opposed to other more Caucasian populations. Admixture analysis showed a higher Mayan genetic component in these patients from Chiapas. CONCLUSIONS: The genetic susceptibility for SLE differed in two populations of Mexican Mestizos with dissimilar ethnic ancestries. Autochthonous Amerindian alleles, and not the more widely known Caucasian alleles, might be associated with the susceptibility to SLE in Mexican Mestizos from Tapachula, Chiapas. Key Points • Autochthonous Amerindian alleles, such as HLA-DRB1*16, had a tendency to be increased in SLE patients, compared to healthy controls. • SLE susceptibility alleles vary considerably among regions in Mexico, according to the distribution of the indigenous groups. • Ethnic admixture is a key determinant in the genetic susceptibility of SLE.

CYP2D6 does not impact on breast cancer-free survival in Southeast Mexican patients under tamoxifen treatment.

Aim: We conducted a retrospective analysis in 71 Mexican Mestizo patients to evaluate the breast cancer-free survival (BCFS) among the inferred genetic phenotypes (GP) of CYP2D6. Patients & methods:CYP2D6 was genotyped through Taqman-probe analysis; GP were inferred according to international guidelines. The BCFS was estimated through Kaplan-Meier method and analyzed with a log-rank test; hazard ratios were calculated with 95% CI and p < 0.05. Results: The BCFS did not differ among CYP2D6 GP (p = 0.45) and recurrence risk was similar between gNM + gUM and gPM + gIM groups (hazard ratio: 1.54, 95% CI: 0.37-6.38; p = 0.55). Conclusion: The findings do not support any impact of CYP2D6 on BCFS. Evaluation of other genetic/nongenetic biomarkers is needed in Mexican Mestizo patients under tamoxifen treatment.

Genotype-Environment Interaction Analysis of NQO1, CYP2E1, and NAT2 Polymorphisms and the Risk of Childhood Acute Lymphoblastic Leukemia: A Report From the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.

Background: Acute lymphoblastic leukemia (ALL) is the main type of cancer in children. In Mexico and other Hispanic populations, the incidence of this neoplasm is one of the highest reported worldwide. Functional polymorphisms of various enzymes involved in the metabolism of xenobiotics have been associated with an increased risk of developing ALL, and the risk is different by ethnicity. The aims of the present study were to identify whether NQO1, CYP2E1, and NAT2 polymorphisms or some genotype-environmental interactions were associated with ALL risk in Mexican children. Methods: We conducted a case-control study including 478 pediatric patients diagnosed with ALL and 284 controls (children without leukemia). Ancestry composition of a subset of cases and controls was assessed using 32 ancestry informative markers. Genetic-environmental interactions for the exposure to hydrocarbons were assessed by logistic regression analysis. Results: The polymorphisms rs1801280 (OR 1.54, 95% CI 1.21-1.93), rs1799929 (OR 1.96, 95% CI 1.55-2.49), and rs1208 (OR 1.44, 95% CI 1.14-1.81) were found to increase the risk of ALL; being the risks higher under a recessive model (OR 2.20, 95% CI 1.30-1.71, OR 3.87, 95% CI 2.20-6.80, and OR 2.26, 95% CI 1.32-3.87, respectively). Gene-environment interaction analysis showed that NAT2 rs1799929 TT genotype confers high risk to ALL under exposure to fertilizers, insecticides, hydrocarbon derivatives, and parental tobacco smoking. No associations among NQO1, CYP2E1, and ALL were observed. Conclusion: Our study provides evidence for the association between NAT2 polymorphisms/gene-environment interactions, and the risk of childhood ALL in Mexican children.

Endoxifen levels and metabolic phenotype-associated factors in Mexican Mestizo patients under tamoxifen treatment.

Aim: To evaluate plasma endoxifen levels and metabolic phenotype-associated factors in Mexican Mestizo patients under tamoxifen treatment. Patients & methods: A total of 138 breast cancer patients under tamoxifen treatment were cross-sectionally evaluated and side effects (SE) were recorded. CYP2D6 genetic phenotypes (GP) and metabolic phenotypes (MP) were assessed (metabolic poor [mPM], intermediate [mIM], normal [mNM], and ultrarapid [mUM] metabolizer). Associations were tested in uni-multivariate models for endoxifen >5.9 ng/ml and for mNM + mUM MP. Results: The main SE was hot flashes (62%). Distribution of the CYP2D6 MP was 4.3% mPM; 14.5% mIM; 75.4% mNM; and 5.8% mUM. Endoxifen >5.9 ng/ml was partially associated with SE (p = 0.06); the mNM + mUM MP was associated with treatment time (p = 0.03). Conclusion: The endoxifen-associated factors in Mexican Mestizo patients remain inconclusive, although treatment time was associated with MP.

Allele diversity of the killer cell immunoglobulin-like receptors KIR3DL1/S1 and the combination with their HLA ligands in Mexican Mestizos from Mexico City.

Killer cell immunoglobulin-like receptors (KIRs), expressed on Natural Killer (NK) cells, activate/inhibit NK cell function through interactions with their HLA-A, B and C ligands. KIR3DL1 is one of the most polymorphic genes and its effect varies depending on the interaction of the specific allotype with its Bw4 ligand. We investigated the allelic diversity of KIR3DL1/S1 using sequence based typing and we typed as well, their Bw4 ligands in Mexican Mestizos of Mexico City. The results showed that this population has a great KIR3DL1 allelic diversity with ∗01502 (19.9%), ∗00101 (13.2%) and ∗00501 (12.8%) being the most common alleles, while KIR3DS1 showed predominance of ∗01301 (86%); these data agree with the diversity found in most populations studied. At least one KIR3DL1-HIGH surface expression allele was present in 67.5% of the subjects. Phylogenetic comparisons between Mestizos and 28 different populations showed that allelic diversity of KIR3DL1/S1 was similar in Mexican Mestizos from Mexico and in Hispanics from USA. Knowledge of KIR and MHC diversity worldwide is fundamental for understanding the impact of KIR and KIR-ligand polymorphism on NK cell effector functions and is relevant in genetic anthropology, disease association and transplantation.

Proficiency of 38 HID-INDELS in kinship analysis and forensic parameters in a Mexican population / Eficiencia de 38 HID-INDELS en análisis de parentesco y parámetros forenses en una población mexicana

Introduction: Insertion–deletions for human identification (HID-INDELs) allow solving peculiar forensic situations when autosomal STRs are insufficient. Although limitations were predicted since the forensic implementation of biallelic markers, formal evaluation of these restrictions is scarce. Particularly, to define the informativity provided by HID-INDELs in kinship analysis is useful to avoid wasting work, resources, and –finally– disappointments.Material and methods: For this reason, we analyzed the 38-plex HID-INDEL system in 25 Mexican families including father, daughter, and mother, whose kinship was previously established with 22 autosomal STRs.Results and discussion: From genotypes of unrelated individuals, we updated allele frequencies and forensic parameters of the Jalisco state (West, Mexico), by increasing the population sample size from 62 to 112. Among the forensic a priori parameters, the Typical paternity index (PI) of the 38plex HID-INDEL system showed important differences regarding the PI and probability of paternity (W) estimated herein from real paternity cases, generally undervaluing the observed informativity of these 38-plex HID-INDEL system. Conversely, the studied HID-INDEL loci offered confident kinship conclusions based on the paternity index (PI ≥10,000) and probability of paternity (W ≥ 99.99%) in 68% of the standard trio cases (18/25), and only 12% of duo paternity cases (6/50) (motherless and fatherless). In fact, 14% of duo paternity cases (7/50) did not reach minimum requirements to stablish paternity (IP < 100; W < 99%).Conclusions: We updated a Mexican population database for 38 HID-INDEL loci, and we described their proficiency from real paternity cases, detailing some limitations non-previously specified. (AU)

Introducción: Las inserciones-deleciones para identificación humana (HID-INDEL), permiten resolver situaciones forenses peculiares cuando los STR autosómicos son insuficientes. Aunque se predijeron sus limitaciones desde la implementación forense de marcadores bialélicos, la evaluación formal de estas restricciones es escasa. Particularmente es útil definir su informatividad en el análisis de parentesco, para evitar desperdiciar trabajo, recursos y –finalmente– decepciones.Material y Métodos: Por este motivo, analizamos el sistema de 38plex HID-INDELs en 25 familias mexicanas entre padre, hija y madre, cuyo parentesco se estableció previamente con 22 STR autosómicos. A partir de los individuos no emparentados, actualizamos las frecuencias alélicas y los parámetros forenses del estado de Jalisco (Oeste, México), aumentando el tamaño de la muestra poblacional de 62 a 112.Resultados y discusión: Entre los parámetros forenses a priori, el índice de paternidad típico (IPT) del sistema 38plex HID-INDEL mostró diferencias importantes con respecto al IP y la probabilidad de paternidad (W) derivados de casos reales de paternidad, generalmente subestimando la informatividad observada de ese sistema. Sin embargo, los 38 HID-INDELs ofrecieron conclusiones de parentesco confiables basadas en el índice de paternidad (IP ≥ 10,000) y la probabilidad de paternidad (W ≥ 99,99%) sólo en el 68% de los casos tríos estándar (18/25), y el 12% de casos de paternidad dúo (6/50) (sin madre y sin padre). De hecho, el 14% de los casos de paternidad dúo (7/50) no alcanzó los requisitos mínimos para establecer la paternidad (IP <100; W < 99%).Conclusiones: En este trabajo actualizamos una base de datos de población mexicana para 38 HID-INDELs y describimos su eficiencia en casos reales de paternidad, detallando algunas limitaciones no especificadas previamente. (AU)

Analysis of ERCC1 and ERCC2 gene variants in osteosarcoma, colorectal and breast cancer.

The Asn118Asn (rs11615) variant in the ERCC1 gene, and the Lys751Gln (rs13181) and Asp312Asn (rs1799793) variants in the ERCC2 gene have been associated with the development of varied types of cancer. The aim of the present study was to test for any association between the ERCC1 and ERCC2 gene variants and three different types of cancer in Mexican-mestizo patients. Patients and their respective controls were formed into three groups: The osteosarcoma group, with 28 patients and 97 controls; the colorectal group, with 108 patients and 119 controls; and the breast cancer group, with 71 patients and 74 controls. Genotyping was performed using TaqMan probes and quantitative polymerase chain reaction. Allele and genotype frequencies were compared using a χ2 test. Only one SNP (rs1799793) was found to be associated with breast cancer. This is the first study analyzing the SNPs in ERCC1 and ERCC2 genes and the susceptibility to cancer in Mexican-mestizo patients with osteosarcoma, and colorectal and breast cancer.

Presence of the HLADR13 allele among Mexican Mestizos suggests a protective factor against relapsing-remitting multiple sclerosis (RRMS).

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic demyelinating disease that affects the central nervous system. Researchers have looked for an association between relapsing-remitting MS (RRMS) and human leukocyte antigen (HLA) as risk or protective factor associated to ethnicity, which may add a partial explanation to disease heterogeneity and geographical variations. We described the frequency of the HLA-DR alleles in Mexican Mestizo (RRMS) patients. PATIENTS AND METHODS: We included 143 RRMS patients and 377 healthy controls, both Mexican Mestizos. Previous signing informed consent, we record demographic and clinical characteristics of the participants. Genetic profile was made, and HLA frequencies in both groups were compared. RESULTS: RRMS patients were 39.8% male and 60.2% female, mean age was 35 years. While, controls were 48%male and 52% women, mean age was 38 years. The most frequent allele found in subjects with RRMS was DR 15 (p=0.006, OR=2.2, 95% CI: 1.3-3.6). DR 13 allele was more frequent among healthy subjects than RRMS patients (p=0.050) with a protective OR 2.6, (95% CI: 1.3-5.2, p=0.050). CONCLUSION: In our study we found HLA DR 13 was more frequent in healthy controls than in RRMS patients, suggesting a protective factor among Mexican Mestizo population.

WHO body mass index for age charts overestimate thinness and overweight compared to international and US charts applied to indigenous and non-indigenous Mexican children

Assessments of whether children are thin (low body mass index for age) or overweight are based on body mass index (BMI for age and sex) charts published by the World Health Organization (WHO), the International Obesity Task Force (IOTF), and the US Centers for Disease Control and Prevention (CDC). We aimed to determine whether these charts indicated different prevalence of thinness and overweight (obesity included) in indigenous and non-indigenous school aged children from different regions and ethnic groups in Mexico. A probability proportional to size, cluster sampling method was employed in four regions of the country. We recruited 1,731 children aged 7.0-9.9 (507 indigenous from six ethnic groups and 1,224 non-indigenous). BMI was calculated according to age, and thinness and overweight classifications were compared according to cutoff values in the WHO, IOTF, and CDC references. The WHO reference generated the highest rates for thinness (12.5%) and overweight (30%) in children across regions and ethnic groups. The CDC reference estimated the lowest rates of thinness in children (5.5%), and the IOTF reference estimated the lowest rates of overweight (24.7%). Estimates of both thinness (8.3%) and overweight (13.4%) rates were lower in indigenous than non-indigenous groups (14.3% and 37.5%, respectively). The WHO BMI for age chart estimated higher rates of thinness and overweight in children compared to the CDC and IOTF charts. Because thinness as indicator of undernutrition status is relatively new, differences in body composition among indigenous and non-indigenous children may justify the need for more appropriate screening criteria to compare the growth status(AU)

La clasificación del estado nutricio de los niños con delgadez o con sobrepeso se realiza empleando el índice de masa corporal (IMC para la edad y el sexo) con las tablas de la OMS, IOTF y CDC. El objetivo de esta investigación fue determinar si estas referencias resultan en diferentes prevalencias de delgadez y sobrepeso (obesidad incluida) en niños escolares indígenas y no indígenas de diferentes regiones de México. Se empleó un muestreo por conglomerados en cuatro regiones del país. Se reclutaron 1,731 niños con edades entre 7,0-9,9 (507 indígenas de cinco grupos étnicos y 1,224 no indigenas) durante 2006 y 2008. El IMC se calculó y se clasificó como delgadez y sobrepeso con los puntos de corte sugeridos por las referencias internacionales. Cuando se compararon las clasificaciones, la referencia de OMS generó la prevalencia más alta de delgadez (12,5%) y sobrepeso (30%) en niños de todas las regiones y grupos étnicos. La referencia de los CDC estimó las prevalencias más bajas de delgadez (5,5%) y la referencia IOTF produjo las proporciones más bajas de sobrepeso (24,7%). Las proporciones de delgadez (8,3%) y sobrepeso (13,4%) fueron más bajas en niños indígenas que en los no indígenas (14.3% y 37.5%, respectivamente). La referencia de la OMS del IMC para la edad produjo las prevalencias más altas de delgadez y sobrepeso en comparación con los estándares de CDC y IOTF. Dado que la delgadez como indicador de desnutrición en niños es de uso reciente, las diferencias encontradas entre indígenas y mestizos pueden justificar el contar con mejores herramientas de tamizaje en estudios de crecimiento(AU)