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Background Focal dermal hypoplasia (FDH) is rare X-linked dominant disease characterized by atrophy and linear pigmentation of the skin, split hand/foot deformities and ocular anomalies. FDH is caused by mutations of the Porcupine (PORCN) gene, which encodes an enzyme that catalyzes the palmitoylation of Wnt ligands required for their secretion. High resolution melting analysis (HRM) is a technique that allows rapid, labor-efficient, low-cost detection of genomic variants. In the present study, we report the successful implementation of HRM in the molecular diagnosis of FDH. Methods Polymerase chain reaction and HRM assays were designed and optimized for each of the coding exons of the PORCN gene, processing genomic DNA samples form a non-affected control and a patient complying with the FDH diagnostic criteria. The causal mutation was characterized by Sanger sequencing from an amplicon showing a HRM trace suggesting heterozygous variation and was validated using an amplification-refractory mutation system (ARMS) assay. Results The melting profiles suggested the presence of a variant in the patient within exon 1. Sanger sequencing revealed a previously unknown C to T transition replacing a glutamine codon for a premature stop codon at position 28, which was validated using ARMS. Conclusions Next-generation sequencing facilitates the molecular diagnosis of monogenic disorders; however, its cost-benefit ratio is not optimal when a single, small or medium size causal gene is already identified and the clinical diagnostic presumption is strong. Under those conditions, as it is the case for FDH, HRM represents a cost- and labor-effective approach.

The forensic value of Y-STR markers in Guine-Bissau was accessed by typing of 215 males. Allele and haplotype frequencies, determined for loci DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439 and the duplicated locus DYS385, are within the limits of variation found in other populations south of the Sahara. The level of discrimination achieved is Guineans is higher than for European or other African populations with comparable data. The haplotype diversity of 0.9995 is reduced to 0.9981 when the minimal haplotype is considered thus revealing the importance of increasing the number of typed loci.

Background The geographic and ethnolinguistic differentiation of many African Y-chromosomal lineages provides an opportunity to evaluate human migration episodes and admixture processes, in a pan-continental context. The analysis of the paternal genetic structure of Equatorial West Africans carried out to date leaves their origins and relationships unclear, and raises questions about the existence of major demographic phenomena analogous to the large-scale Bantu expansions. To address this, we have analysed the variation of 31 binary and 11 microsatellite markers on the non-recombining portion of the Y chromosome in Guinea-Bissau samples of diverse ethnic affiliations, some not studied before. Results The Guinea-Bissau Y chromosome pool is characterized by low haplogroup diversity (D = 0.470, sd 0.033), with the predominant haplogroup E3a*-M2 shared among the ethnic clusters and reaching a maximum of 82.2% in the Mandenka people. The Felupe-Djola and Papel groups exhibit the highest diversity of lineages and harbor the deep-rooting haplogroups A-M91, E2-M75 and E3*-PN2, typical of Sahel's more central and eastern areas. Their genetic distinction from other groups is statistically significant (P = 0.01) though not attributable to linguistic, geographic or religious criteria. Non sub-Saharan influences were associated with the presence of haplogroup R1b-P25 and particular lineages of E3b1-M78. Conclusion The predominance and high diversity of haplogroup E3a*-M2 suggests a demographic expansion in the equatorial western fringe, possibly supported by a local agricultural center. The paternal pool of the Mandenka and Balanta displays evidence of a particularly marked population growth among the Guineans, possibly reflecting the demographic effects of the agriculturalist lifestyle and their putative relationship to the people that introduced early cultivation practices into West Africa. The paternal background of the Felupe-Djola and Papel ethnic groups suggests a better conserved ancestral pool deriving from East Africa, from where they have supposedly migrated in recent times. Despite the overall homogeneity in a multiethnic sample, which contrasts with their social structure, minor clusters suggest the imprints of multiple peoples at different timescales: traces of ancestral inhabitants in haplogroups A-M91 and B-M60, today typical of hunter-gatherers; North African influence in E3b1-M78 Y chromosomes, probably due to trans-Saharan contacts; and R1b-P25 lineages reflecting European admixture via the North Atlantic slave trade.