High incidence of AZF duplications in clan-structured Iranian populations detected through Y chromosome sequencing read depth analysis.

The ampliconic region of the human Y chromosome consists of large duplicated sequences that can undergo non-allelic homologous recombination (NAHR), resulting in structural rearrangements that may cause infertility, especially when they occur in the azoospermia factor b/c (AZFb/c) region. Although AZF duplications have long been neglected due to the technical limitations of STS-based studies that focused mainly on deletions, recent next generation sequencing (NGS) technologies provided evidence for their importance in fertility. In this study, a NGS read depth approach was used to detect AZFb/c rearrangements in 87 Iranians from different ethnic groups. The duplication frequency in Iran proved to be twice as high as in the "1000 Genomes" dataset. Interestingly, most duplications were found in patrilineal ethnic groups, possibly as a consequence of their lower male effective population size which can counteract negative selection. Moreover, we found a large 8.0 Mb duplication, resulting in a fourfold increase in the copy number of AZFc genes, which to our knowledge is the largest duplication ever reported in this region. Overall, our results suggest that it is important to consider not only AZF deletions but also duplications to investigate the causes of male infertility, especially in patrilineal clan-based populations.

The genomic echoes of the last Green Sahara on the Fulani and Sahelian people.

The population history of the Sahara/Sahelian belt is understudied, despite previous work highlighting complex dynamics.1,2,3,4,5,6,7 The Sahelian Fulani, i.e., the largest nomadic pastoral population in the world,8 represent an interesting case because they show a non-negligible proportion of an Eurasian genetic component, usually explained by recent admixture with northern Africans.1,2,5,6,7,9,10,11,12 Nevertheless, their origins are largely unknown, although several hypotheses have been proposed, including a possible link to ancient peoples settled in the Sahara during its last humid phase (Green Sahara, 12,000-5,000 years before present [BP]).13,14,15 To shed light about the Fulani ancient genetic roots, we produced 23 high-coverage (30×) whole genomes from Fulani individuals from 8 Sahelian countries, plus 17 samples from other African groups and 3 from Europeans as controls, for a total of 43 new whole genomes. These data have been compared with 814 published modern whole genomes2,16,17,18 and with relevant published ancient sequences (> 1,800 samples).19 These analyses showed some evidence that the non-sub-Saharan genetic ancestry component of the Fulani might have also been shaped by older events,1,5,6 possibly tracing the Fulani origins to unsampled ancient Green Saharan population(s). The joint analysis of modern and ancient samples allowed us to shed light on the genetic ancestry composition of such ancient Saharans, suggesting a similarity with Late Neolithic Moroccans and possibly pointing to a link with the spread of cattle herding. We also identified two different Fulani clusters whose admixture pattern may be informative about the historical Fulani movements and their later involvement in the western African empires.

Improving discrimination capacity through rapidly mutating Y-STRs in structured populations from the African continent.

Y chromosome short tandem repeats (Y-STRs) typing is becoming increasingly popular in forensic casework mainly because it allows the recovery of male-specific genetic information from severely unbalanced male-female DNA mixtures. The relatively low discrimination power of conventional Y-STR multiplexes, due to linkage disequilibrium among polymorphic loci, has been partially overcome by the introduction of rapidly mutating Y microsatellites (RM Y-STRs) with mutation rates exceeding 1 × 10-2/generation. In previous works, we reported an unexpectedly high level of haplotype sharing among African males using the Yfiler Plus PCR Amplification kit, the most powerful commercially available system, including 19 conventional Y-STRs and 6 RM Y-STRs. In particular, analyzing 1370 males from northern, eastern and central Africa, 240 subjects were found to share 100 Y-STR haplotypes. We attributed the relatively low discrimination capacity to several factors including patrilocality, endogamy, sampling bias and degree of urbanization. In the present study, using a blind search analysis based on 16 autosomal STRs, we first investigated the kinship between pairs of African males previously found to share the Yfiler Plus haplotype; then, we evaluated the improvement in identification capacity allowed by a PCR multiplex assay (RM-YPlex) based on 13 "first generation" RM Y-STR, seven of which are not included in the Yfiler Plus multiplex. Among 228 pairs of males sharing a Yfiler Plus haplotype, we detected 134 related (cousins or closer) and 94 unrelated (or distantly related) pairs of subjects. By using the RM-YPlex, we observed a full genotype concordance for the six loci shared with the Yfiler Plus, while the additional seven RM Y-STRs allowed the discrimination among 58.2 % related pairs and 84.0 % unrelated pairs. The discrimination capacity increased from 0.898 to 0.958, while the proportion of males sharing a haplotype decreased from 17.5 % to 8.0 %. These findings further highlight the capability of RM Y-STRs to distinguish males even in close kinship scenarios and in sub-structured populations as African ones, but at the same time call for the discovery and testing of additional RM Y-STRs to fully differentiate male relatives.

Intake of food groups and cervical cancer in women at risk for cervical cancer: A nested case-control study.

Background: The risk of cervical cancer was reported to be influenced by dietary components. This study aimed to illustrate the association between cervical cancer with the intake of food groups in women with a history of cervical neoplasia. Methods: This nested case-control study was conducted in 558 people with a history of cervical intraepithelial neoplasia (CIN), including 279 women with cervical cancers and 279 controls with low-grade squamous intraepithelial lesions (LSIL). A validated food frequency questionnaire (FFQ) was used to assess the intake of food groups. Results: The intake of fruits and vegetables in the case group was significantly lower than the control group (P=0.001). Low intake of dairy products, vegetables, and fruits was associated with cervical cancer risk (OR=4.67; 95% CI 1.2-9.49, P=0.001; OR=9.75, 95% CI 1.36-19. 51, P=0.001; and OR=4.82, 95% CI 1.09-7.25, P=0.001, respectively). After adjusting for age, family history, age at first menstruation, number of children, history of vaginal infection, and age at first sexual intercourse, the results were still significant. Additional adjustments to BMI did not change the results. Conclusion: The results indicate that the risk of cervical cancer can be affected by the intake of certain food groups. Further longitudinal studies are needed to confirm these findings and determine the underlying mechanism of the influence of dietary components on cervical cancer risk.

Interactions of Colorectal Cancer, Dietary Fats, and Polymorphisms of Arachidonate Lipoxygenase and Cyclooxygenase Genes: A Literature Review.

Objective: Genetics and dietary factors play important roles in the development of colorectal cancer (CRC). However, the underlying mechanisms of the interactions between CRC, gene polymorphisms, and dietary fat are unclear. This review study investigated the effects of polymorphisms of arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) genes in the association between CRC and dietary fat. Methods: All the related papers published from 2000 to 2022 were collected from different databases such as PubMed, Science Direct, Scopus, and Cochran using related keywords such as colorectal cancer, ALOX, COX, polymorphism, and dietary fat. Non-English and unrelated documents were excluded. Results: Some single-nucleotide polymorphisms (SNPs) in the ALOX and COX genes, such as rs2228065, rs6413416, and rs4986832 in the ALOX gene, and rs689465 in the COX gene may play significant roles in the association between the risk of CRC and dietary fats. SNPs of ALOX and COX genes may influence the effects of dietary fatty acids on the risk of CRC. Conclusion: Some polymorphisms of the ALOX and COX genes may have important roles in the effects of dietary fat on the risk of CRC. If future studies confirm these results, dietary recommendations for preventing colorectal cancer may be personalized based on the genotype of the ALOX and COX genes.

The effect of methylenetetrahydrofolate reductase polymorphisms on susceptibility to human papilloma virus infection and cervical cancer.

Cervical cancer is the third most common cancer among women worldwide. Several factors lead to cervical cancer, among which human papilloma virus (HPV) infection has a prominent role. Methylenetetrahydrofolate reductase (MTHFR) is crucial in folate metabolic pathway and plays an important role in DNA synthesis and DNA methylation. MTHFR gene polymorphisms, including C677T and A1298C, lead to reduced enzyme activity. This case-control study aims to illustrate the association between MTHFR gene polymorphisms and the risk of cervical cancer. This study was conducted on 196 samples, which included 96 cervical biopsy samples compared to 100 Pap smear samples of normal healthy women without HPV infection. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the MTHFR polymorphism detection, followed by fluorescent amplification-based specific hybridization PCR method to detect HPV16 and HPV18. The results show that the MTHFR 677TT genotype plays a protective role in cervical cancer (P=0.0030) (OR=0.21, 95% confidence interval [CI]: 0.07-0.59). Furthermore, there was a strong significant association between MTHFR 1298CC genotype and the risk of cervical cancer (OR=10.69; 95% CI: 4.28-26.71, P=0.0001). It can be concluded that A1298C polymorphism is a genetic risk factor for cervical cancer in the assessed Iranian population group. It seems that MTHFR 1298CC genotype is more susceptible to HPV 16 infection. Combination analysis of MTHFR C677T and A1298C polymorphisms revealed that combined MTHFR 677CC and 1298CC are strongly associated with a risk of cervical cancer.