Inter and intra-island genetic structure and differentiation of the endemic Bolle's Laurel Pigeon (Columba bollii) in the Canary archipelago.

Islands provide excellent settings for studying the evolutionary history of species, since their geographic isolation and relatively small size limit gene flow between populations, and promote divergence and speciation. The endemic Bolle's Laurel Pigeon Columba bollii is an arboreal frugivorous bird species distributed on laurel forests in four islands of the Canary archipelago. To elucidate the population genetics, we genotyped ten microsatellite loci using DNA obtained from non-invasive samples collected across practically all laurel forest remnants, and subsequently grouped into eight sampling sites. Analyses including F-statistics, Bayesian clustering approaches, isolation by distance tests and population graph topologies, were used to infer the genetic diversity and the population differentiation within and among insular populations. Additionally, we evaluated the effect of null alleles on data analysis. Low genetic diversity was found in all populations of Bolle's Laurel Pigeon, with no significant differences in diversity among them. However, significant genetic differentiation was detected among all populations, with pigeons from La Palma and El Hierro exhibiting the closest affinity. Bayesian clustering supported population separation between islands, and also detected fine-scale structure within the Tenerife and La Gomera populations. Our results suggest that, despite columbids have a high movement ability, they can show signature of genetic divergence among populations, particularly on oceanic islands. Geological history of the islands and distribution range of habitats could have close influence on the evolutionary trajectories of these birds. This approach can provide practical tools to implement appropriate conservation measures for range-restricted species and their habitat.

Sex-specific viability effects of mutations in Drosophila melanogaster.

In populations with separate sexes, genetic load due to deleterious mutations may be expressed differently in males and females. Evidence from insect models suggests that selection against mutations is stronger in males. This pattern will reduce deleterious allele frequencies at the expense of males, such that female mean fitness is greater than expected, preserving population persistence in the face of high mutation rates. While previous studies focus on reproductive success, mutation load depends on total selection in each sex, including selection for viability. We might expect minimal sex differences in viability effects in fruit flies, since male and female larvae behave similarly, yet many genes show sex-biased expression in larvae. We measured the sex-specific viability effects of nine "marker" mutations and 123 mutagenized chromosomes. We find that both types of mutations generally reduce viability in both sexes. Among marker mutations we detect instances of sex biased effects in each direction; mutagenized chromosomes show little sex-specific mutational variance, but recessive lethals show a female bias, including in FlyBase records. We conclude that mutations regularly affect viability in a sex-specific manner, but that the strong pattern of male-biased mutational effects observed previously for reproductive success is not apparent at the pre-reproductive stage.

Identification of novel bovine leukocyte antigen alleles and association of BoLA-DRB3.2*020:02:01 with resistance to Theileria orientalis infection in crossbred Kedah-Kelantan cattle: a pilot study.

The bovine leukocyte antigen (BoLA) gene is a significant genetic part of the immune system and has been used as a disease marker in cattle. In this study, we detected Theileria orientalis, T. sinensis, Anaplasma marginale, Anaplasma platys, Candidatus Mycoplasma haemobos and Trypanosoma evansi by PCR amplification and sequencing of the amplicons. The allelic association of the BoLA-DRB3.2 gene with blood pathogen disease resistance and susceptibility in 87 Kedah-Kelantan x Brahman (KKB) and 38 Bali cattle was determined by Fisher's exact test and Cochran Mantel Haenszel (CMH) correction test. Sequence-based typing of the BoLA-DRB3.2 gene identified 43 alleles (27 previously reported alleles and 16 novel alleles) across the two cattle breeds. Alignment analysis of the 16 novel alleles revealed 90.7-95.8% and 85-92% nucleotide and amino acid identities, with the reference allele, BoLA-DRB3*016:01 cDNA clone NR-1. BoLA-DRB3*009:02 (25.6%) and BoLA-DRB3*036:01 (36%) were the most frequent alleles in KKB and Bali cattle, respectively. In KKB cattle, BoLA-DRB3*020:02:01 was significantly associated with resistance to T. orientalis whereas *007:01 and *009:02 were significantly associated with resistance to C. Mycoplasma haemobos. Also, DRB3*017:01 was associated with susceptibility to T. orientalis in KKB cattle. In the Bali cattle, BoLA-DRB3*015:01 was found to be a genetic marker of susceptibility to C. Mycoplasma haemobos infection. Therefore, this study identified BoLA-DRB3.2 alleles associated with resistance and susceptibility to T. orientalis infection in KKB cattle and susceptibility to C. Mycoplasma haemobos infection in Bali cattle for the first time. Therefore, this study suggests that these BoLA-DRB3 resistance alleles could be used as candidate markers for selection, whereas susceptibility alleles could be used as candidate markers for culling in the beef industry.

Association between Complex ACTN3 and ACE Gene Polymorphisms and Elite Endurance Sports in Koreans: A Case-Control Study.

ACTN3 R577X and ACE I/D polymorphisms are associated with endurance exercise ability. This case-control study explored the association of ACTN3 and ACE gene polymorphisms with elite pure endurance in Korean athletes, hypothesizing that individuals with both ACTN3 XX and ACE II genotypes would exhibit superior endurance. We recruited 934 elite athletes (713 males, 221 females) and selected 45 pure endurance athletes (36 males, 9 females) requiring "≥90% aerobic energy metabolism during sports events", in addition to 679 healthy non-athlete Koreans (361 males, 318 females) as controls. Genomic DNA was extracted and genotyped for ACTN3 R577X and ACE I/D polymorphisms. ACE ID (p = 0.090) and ACTN3 RX+XX (p = 0.029) genotype distributions were significantly different between the two groups. Complex ACTN3-ACE genotypes also exhibited significant differences (p = 0.014), with dominant complex genotypes positively affecting endurance (p = 0.039). The presence of RX+II or XX+II was associated with a 1.763-fold higher likelihood of possessing a superior endurance capacity than that seen in healthy controls (90% CI = 1.037-3.089). Our findings propose an association of combined ACTN3 RX+XX and ACE II genotypes with enhanced endurance performance in elite Korean athletes. While causality remains to be confirmed, our study highlights the potential of ACTN3-ACE polymorphisms in predicting elite endurance.

SeqSNP-Based Targeted GBS Provides Insight into the Genetic Relationships among Global Collections of Brassica rapa ssp. oleifera (Turnip Rape).

Turnip rape is a multi-purpose crop cultivated in temperate regions. Due to its ability to fit into crop rotation systems and its role as a food and feed source, spring-type turnip rape cultivation is on the rise. To improve the crop's productivity and nutritional value, it is essential to understand its genetic diversity. In this study, 188 spring-type accessions were genotyped using SeqSNP, a targeted genotyping-by-sequencing method to determine genetic relationships between various groups and assess the potential effects of mutations within genes regulating major desirable traits. Single nucleotide polymorphism (SNP) alleles at six loci were predicted to have high effects on their corresponding genes' functions, whereas nine loci had country/region-specific alleles. A neighbor-joining cluster analysis revealed three major clusters (I to III). About 72% of cluster-I accessions were of Asian origin, whereas 88.5% of European accessions and all North American accessions were placed in cluster-II or cluster-III. A principal coordinate analysis explained 65.3% of the total genetic variation. An analysis of molecular variance revealed significant differentiation among different groups of accessions. Compared to Asian cultivars, European and North American cultivars share more genetic similarities. Hence, crossbreeding Asian and European cultivars may result in improved cultivars due to desirable allele recombination. Compared to landraces and wild populations, the cultivars had more genetic variation, indicating that breeding had not caused genetic erosion. There were no significant differences between Swedish turnip rape cultivars and the NordGen collection. Hence, crossbreeding with genetically distinct cultivars could enhance the gene pool's genetic diversity and facilitate superior cultivar development.

Machine Learning-Driven Prediction of Brain Age for Alzheimer's Risk: APOE4 Genotype and Gender Effects.

Background: Alzheimer's disease (AD) is a leading cause of dementia, and it is significantly influenced by the apolipoprotein E4 (APOE4) gene and gender. This study aimed to use machine learning (ML) algorithms to predict brain age and assess AD risk by considering the effects of the APOE4 genotype and gender. Methods: We collected brain volumetric MRI data and medical records from 1100 cognitively unimpaired individuals and 602 patients with AD. We applied three ML regression models-XGBoost, random forest (RF), and linear regression (LR)-to predict brain age. Additionally, we introduced two novel metrics, brain age difference (BAD) and integrated difference (ID), to evaluate the models' performances and analyze the influences of the APOE4 genotype and gender on brain aging. Results: Patients with AD displayed significantly older brain ages compared to their chronological ages, with BADs ranging from 6.5 to 10 years. The RF model outperformed both XGBoost and LR in terms of accuracy, delivering higher ID values and more precise predictions. Comparing the APOE4 carriers with noncarriers, the models showed enhanced ID values and consistent brain age predictions, improving the overall performance. Gender-specific analyses indicated slight enhancements, with the models performing equally well for both genders. Conclusions: This study demonstrates that robust ML models for brain age prediction can play a crucial role in the early detection of AD risk through MRI brain structural imaging. The significant impact of the APOE4 genotype on brain aging and AD risk is also emphasized. These findings highlight the potential of ML models in assessing AD risk and suggest that utilizing AI for AD identification could enable earlier preventative interventions.

Impact of HLA Alleles on COVID-19 Severity in Kidney Transplant Recipients: A Single-Center Study.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global health, particularly affecting vulnerable populations, such as organ transplant recipients. Human leukocyte antigens (HLAs) play a critical role in immune response regulation, and understanding their association with COVID-19 can provide insights into disease susceptibility and severity. This study aims to explore the association between HLA allele variability and COVID-19 susceptibility and severity among kidney transplant recipients. Methods In 2023, we conducted a study on 73 kidney transplant recipients who tested positive for COVID-19 via polymerase chain reaction. This study included assessments of clinical status, immunosuppressive drug levels, HLA allele frequencies, and donor-recipient tissue compatibility. Molecular analyses were performed using sequence-specific oligonucleotide typing, and statistical analysis was conducted using IBM SPSS Statistics, version 20.0 (IBM Corp., Armonk, NY). Results Among the participants, 31 were hospitalized and 42 were treated as outpatients. Significant differences were observed in HLA allele distributions, particularly the HLA-A*11 allele, which was more prevalent in outpatient-treated patients, suggesting a potential protective effect. No significant age differences were observed between hospitalized and outpatient groups. Serum tacrolimus levels were notably higher in outpatients. Statistical analyses revealed significant associations between certain HLA groups and the severity of COVID-19 infection. Conclusions This study highlights the importance of HLA allele compatibility in influencing the clinical outcomes of COVID-19 in kidney transplant recipients. The findings suggest that specific HLA alleles may reduce susceptibility or moderate the severity of COVID-19, indicating a need for broader genetic studies across diverse populations to validate these observations and improve management strategies for transplant recipients during pandemics.

A prioritization tool for cilia-associated genes and their in vivo resources unveil new avenues for ciliopathy research.

Defects in ciliary signaling or mutations in proteins that localize to primary cilia lead to a class of human diseases known as ciliopathies. About 10% of mammalian genes encode cilia-associated proteins and a major gap in the cilia research field is prioritizing which genes to study and finding the in vivo vertebrate mutant alleles and reagents available for their study. Here we present a unified resource listing the cilia-associated human genes cross-referenced to available mouse and zebrafish mutant alleles, their associated phenotypes as well as expression data in kidney and functional data for vertebrate Hedgehog signaling. This resource empowers researchers to easily sort and filter genes based on their own expertise and priorities, cross-reference with newly-generated -omics datasets, and quickly find in vivo resources and phenotypes associated with a gene of interest.

The molecular basis of lactase persistence: Linking genetics and epigenetics.

Lactase persistence (LP) - the genetic trait that determines the continued expression of the enzyme lactase into adulthood - has undergone recent, rapid positive selection since the advent of animal domestication and dairying in some human populations. While underlying evolutionary explanations have been widely posited and studied, the molecular basis of LP remains less so. This review considers the genetic and epigenetic bases of LP. Multiple single-nucleotide polymorphisms (SNPs) in an LCT enhancer in intron 13 of the neighbouring MCM6 gene are associated with LP. These SNPs alter binding of transcription factors (TFs) and likely prevent age-related increases in methylation in the enhancer, maintaining LCT expression into adulthood to cause LP. However, the complex relationship between the genetics and epigenetics of LP is not fully characterised, and the mode of action of methylation quantitative trait loci (meQTLs) (SNPs affecting methylation) generally remains poorly understood. Here, we examine published LP data to propose a model describing how methylation in the LCT enhancer is prevented in LP adults. We argue that this occurs through altered binding of the TF Oct-1 (encoded by the gene POU2F1) and neighbouring TFs GATA-6 (GATA6), HNF-3A (FOXA1) and c-Ets1 (ETS1) acting in concert. We therefore suggest a plausible new model for LCT downregulation in the context of LP, with wider relevance for future work on the mechanisms of other meQTLs.

Genetic association of antinuclear antibodies with HLA in JIA patients: a Swedish cohort study.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition. METHODS: We analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm. RESULTS: Case-control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to HLA-DQA1 and HLA-DRB1. HLA-DRB1*08:01, HLA-DQA1*04:01, and HLA-DQB1*04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the HLA-DRB1-DQA1-DQB1 haplotype, our analysis suggests that HLA-DRB1*08 might be the primary allele linked to JIA susceptibility. The HLA-DRB1*11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the HLA-DRB1-DQA1-DQB1 haplotype, HLA-DRB1*11, and HLA-DPB1*02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity. CONCLUSIONS: This study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.

Allelic variability in the Rpp1 locus conferring resistance to Asian soybean rust revealed by genome-wide association.

Soybean is a crucial crop for the Brazilian economy, but it faces challenges from the biotrophic fungus Phakopsora pachyrhizi, which causes Asian Soybean Rust (ASR). In this study, we aimed to identify SNPs associated with resistance within the Rpp1 locus, which is effective against Brazilian ASR populations. We employed GWAS and re-sequencing analyzes to pinpoint SNP markers capable of differentiating between soybean accessions harboring the Rpp1, Rpp1-b and other alternative alleles in the Rpp1 locus and from susceptible soybean cultivars. Seven SNP markers were found to be associated with ASR resistance through GWAS, with three of them defining haplotypes that efficiently distinguished the accessions based on their ASR resistance and source of the Rpp gene. These haplotypes were subsequently validated using a bi-parental population and a diverse set of Rpp sources, demonstrating that the GWAS markers co-segregate with ASR resistance. We then examined the presence of these haplotypes in a diverse set of soybean genomes worldwide, finding a few new potential sources of Rpp1/Rpp1-b. Further genomic sequence analysis revealed nucleotide differences within the genes present in the Rpp1 locus, including the ULP1-NBS-LRR genes, which are potential R gene candidates. These results provide valuable insights into ASR resistance in soybean, thus helping the development of resistant soybean varieties through genetic breeding programs.

Influence of selection on the probability of fixation at a locus with multiple alleles.

BACKGROUND: Genes exist in a population in a variety of forms (alleles), as a consequence of multiple mutation events that have arisen over the course of time. In this work we consider a locus that is subject to either multiplicative or additive selection, and has n alleles, where n can take the values 2, 3, 4, … . We focus on determining the probability of fixation of each of the n alleles. For n = 2 alleles, analytical results, that are 'exact', under the diffusion approximation, can be found for the fixation probability. However generally there are no equally exact results for n ≥ 3 alleles. In the absence of such exact results, we proceed by finding results for the fixation probability, under the diffusion approximation, as a power series in scaled strengths of selection such as R i , j = 2 N e ( s i - s j ) , where N e is the effective population size, while s i and s j are the selection coefficients associated with alleles i and j, respectively. RESULTS: We determined the fixation probability when all terms up to second order in the R i , j are kept. The truncation of the power series requires that the R i , j cannot be indefinitely large. For magnitudes of the R i , j up to a value of approximately 1, numerical evidence suggests that the results work well. Additionally, results given for the particular case of n = 3 alleles illustrate a general feature that holds for n ≥ 3 alleles, that the fixation probability of a particular allele depends on that allele's initial frequency, but generally, this fixation probability also depends on the initial frequencies of other alleles at the locus, as well as their selective effects. CONCLUSIONS: We have analytically exposed the leading way the probability of fixation, at a locus with multiple alleles, is affected by selection. This result may offer important insights into CDCV traits that have extreme phenotypic variance due to numerous, low-penetrance susceptibility alleles.

NOD alleles at Idd1 and Idd2 loci drive exocrine pancreatic inflammation.

Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes and have enabled the identification of several loci associated with diabetes susceptibility, termed insulin-dependent diabetes (Idd). The generation of congenic mice has allowed the characterization of the impact of several loci on disease susceptibility. For instance, NOD.B6-Idd1 and B6.NOD-Idd1 congenic mice were instrumental in demonstrating that susceptibility alleles at the MHC locus (known as Idd1) are necessary but not sufficient for autoimmune diabetes progression. We previously showed that diabetes resistance alleles at the Idd2 locus provide significant protection from autoimmune diabetes onset, second to Idd1. In search of the minimal genetic factors required for T1D onset, we generated B6.Idd1.Idd2 double-congenic mice. Although the combination of Idd1 and Idd2 is not sufficient to induce diabetes onset, we observed immune infiltration in the exocrine pancreas of B6.Idd2 mice, as well as an increase in neutrophils and pancreatic tissue fibrosis. In addition, we observed phenotypic differences in T-cell subsets from B6.Idd1.Idd2 mice relative to single-congenic mice, suggesting epistatic interaction between Idd1 and Idd2 in modulating T-cell function. Altogether, these data show that Idd1 and Idd2 susceptibility alleles are not sufficient for autoimmune diabetes but contribute to inflammation and immune infiltration in the pancreas.

Extending HLA allele sequences using next-generation sequencing technology.

Extended sequences for 13 HLA alleles were found which had limited coverage previously.

The newly characterised HLA-B*41:84 allele, found in a prospective liver transplant candidate.

HLA-B*41:84 has a single base substitution in exon 2, altering glutamic acid to glutamine'.

Genome characterization of a multi-drug resistant Escherichia coli strain, L1PEag1, isolated from commercial cape gooseberry fruits (Physalis peruviana L.).

Introduction: Foodborne infections, which are frequently linked to bacterial contamination, are a serious concern to public health on a global scale. Whether agricultural farming practices help spread genes linked to antibiotic resistance in bacteria associated with humans or animals is a controversial question. Methods: This study applied a long-read Oxford Nanopore MinION-based sequencing to obtain the complete genome sequence of a multi-drug resistant Escherichia coli strain (L1PEag1), isolated from commercial cape gooseberry fruits (Physalis peruviana L.) in Ecuador. Using different genome analysis tools, the serotype, Multi Locus Sequence Typing (MLST), virulence genes, and antimicrobial resistance (AMR) genes of the L1PEag1 isolate were determined. Additionally, in vitro assays were performed to demonstrate functional genes. Results: The complete genome sequence of the L1PEag1 isolate was assembled into a circular chromosome of 4825.722 Kbp and one plasmid of 3.561 Kbp. The L1PEag1 isolate belongs to the B2 phylogroup, sequence type ST1170, and O1:H4 serotype based on in silico genome analysis. The genome contains 4,473 genes, 88 tRNA, 8 5S rRNA, 7 16S rRNA, and 7 23S rRNA. The average GC content is 50.58%. The specific annotation consisted of 4,439 and 3,723 genes annotated with KEEG and COG respectively, 3 intact prophage regions, 23 genomic islands (GIs), and 4 insertion sequences (ISs) of the ISAs1 and IS630 families. The L1PEag1 isolate carries 25 virulence genes, and 4 perfect and 51 strict antibiotic resistant gene (ARG) regions based on VirulenceFinder and RGI annotation. Besides, the in vitro antibiotic profile indicated resistance to kanamycin (K30), azithromycin (AZM15), clindamycin (DA2), novobiocin (NV30), amikacin (AMK30), and other antibiotics. The L1PEag1 isolate was predicted as a human pathogen, matching 464 protein families (0.934 likelihood). Conclusion: Our work emphasizes the necessity of monitoring environmental antibiotic resistance, particularly in commercial settings to contribute to develop early mitigation techniques for dealing with resistance diffusion.

Eight new variants of HLA-DQB1*03 identified by next-generation sequencing.

Genomic sequence of HLA-DQB1*03:01:01:60, -DQB1*03:01:01:61, -DQB1*03:01:01:62, -DQB1*03:01:01:63, -DQB1*03:02:01:23, -DQB1*03:02:01:24, -DQB1*03:02:01:25 and -DQB1*03:03:02:14 alleles in Spanish individuals.

Identification of a novel RHCE*Ce (829G > A) allele associated with absence of C and e antigens expression.

BACKGROUND: The Rh blood group antigens are encoded by the RHD and RHCE genes, which possess a remarkable degree of polymorphism owing to their high homologous structures. These variants of the RH genes can lead to absence or weak expression of antigens. METHODS: Analysis of RHCE genotyping by Polymerase Chain Reaction (PCR-SSP) method specific to detect c.48G, c.48C, 109 bp insertion of IVS2, c.201A and c.307C and RhCE phenotyping, were conducted in 316 Chinese patients in previous study. One patient with discrepancy typing result was collected for further RhCE serologic typing using microcolumn gel method and tube method in saline using monoclonal antibodies. PacBio sequencing was performed for RHCE, RHD and RHAG complete sequence analysis. 3D molecular models of the protein with the wild-type and mutant residue were generated using the DynaMut web server. The effect of the mutation on the protein function was predicted by PolyPhen-2 software. RESULTS: One male patient of Chinese Han was detected with RHCE*C allele showed by PCR-SSP method but ccEE phenotype. Further PacBio sequencing identified one normal RHCE*cE allele and one RHCE*Ce allele carried a novel c.829G > A (p.Gly277Arg) variant, which the encoded amino acid located in the ninth transmembrane segment of RhCE protein. Crystallisation analysis of 3D molecular models revealed that the substitution at Arg277 leads to the formation of additional hydrogen bonds, including weak hydrogen bonds between multiple atoms. It also results in hydrophobic ion interactions between Arg277 and Ala244. This mutation is predicted to have a damaging effect on protein function. CONCLUSION: One novel RHCE*Ce allele with c.829G > A (p.Gly277Arg) variant was identified to resulting in the absence or weak expression of C and e antigens.

Genetic Markers of Acute Childhood B-Lineage Lymphoblastic Leukemia in the Kazakh Population.

INTRODUCTION: To investigate the genetic contribution of 24 GWAS-associated polymorphic gene variants on the development of children's B-lineage acute lymphoblastic leukemia (B-ALL) in an ethnically homogeneous population of Kazakhs. METHODS: A study of 205 children with B-ALL and 204 healthy children was conducted. Genotyping of polymorphic loci was carried out using the TaqMan method. RESULTS: Significant associations (p < 0.05) with the risk of childhood B-ALL were found for twelve variants, including rs6457327 of the HLA gene, rs4251961 of the IL1RN gene, and rs1800630 of the TNF gene. Carriage of the minor allele A of the protective rs1801157 polymorphism A of the CXCL12 gene reduces the risk of B-ALL in the Kazakh population by 40%. DISCUSSION: The results reveal significant associations of polymorphic genetic variants, which can serve as a basis for the development of effective methods for predicting the risk of B-ALL, early diagnosis, and timely treatment.

After an initial Hermansky-Pudlak syndrome clinical diagnosis, molecular testing reveals variants for oculocutaneous albinism type 1B: A case report.

BACKGROUND: Albinism is a heterogeneous condition in which patients present complete absence, reduction, or normal pigmentation in skin, hair and eyes in addition to ocular defects. One of the heterogeneous forms of albinism is observed in Hermansky-Pudlak syndrome (HPS) patients. HPS is characterized by albinism and hemorrhagic diathesis due to the absence of dense bodies in platelets. METHODS: In this report, we describe a case of a pair of Puerto Rican siblings with albinism that were clinically diagnosed with HPS during childhood. Since they did not harbor the founder changes in the HPS1 and HPS3 genes common in Puerto Ricans, as adults they wanted to know the type of albinism they had. We performed exome sequencing, validation by PCR, and cloning of PCR products followed by Sanger sequencing in the family members. RESULTS: We discovered no mutations that could explain an HPS diagnosis. Instead, we found the siblings were compound heterozygotes for 4 variants in the Tyrosinase gene: c.-301C>T, c.140G>A (rs61753180; p.G47D), c.575C>A (rs1042602; p.S192Y), and c.1205G>A (rs1126809; p.R402Q). Our results show that the correct diagnosis for the siblings is OCA1B. CONCLUSION: Our study shows the importance of molecular testing when diagnosing a rare genetic disorder, especially in populations were the disease prevalence is higher.