Geographical and linguistic structure in the people of Kenya demonstrated using 21 autosomal STRs.

Kenya is a diverse and populous nation that employs DNA evidence in its criminal justice system, and therefore requires reliable information on autosomal STR allele frequency variation across the country and in its many ethnic groups. In order to provide reference data and to assess population structure, we analysed the 21 autosomal STRs in the GlobalFiler multiplex in a sample of 510 indigenous Kenyans representing the country's eight former provinces, 43 of its 47 counties, three main linguistic families and all 29 ethnic groups that each comprise >0.5% of the 2019 census population. The indigenous population originated from successive migrations of Cushitic, Nilotic and Bantu speaking groups who settled in regions that suited their distinctive sustenance lifestyles. Consequently, they now largely reside in a patchwork of communities with strong associations with particular counties and provinces and limited degrees of inter-group marriage, as shown by DNA donors' ancestry details. We found significant genetic differentiation between the three Nilotic language sub-families, with Western Nilotes (the Luo ethnic group) showing greater similarity to the Bantu than the Southern and Eastern Nilotes which themselves showed closer affinity to the Cushitic speakers. This concurs with previous genetic, linguistic and social studies. Comparisons with other African populations also showed that linguistic affiliation is a stronger factor than geography. This study revealed several rare off-ladder alleles whose structure was determined by Sanger sequencing. Among the unusual features that could affect profile interpretation were a deletion of Amelogenin Y but no other forensic marker (autosomal or Y-chromosomal), a triallelic pattern at TPOX and an extremely short SE33 allele falling within the expected size range of D7S820. Compared with the currently implemented Identifiler multiplex, Random Match Probabilities decreased from 6.4 × 10-19 to 3.9 × 10-27. The appreciation of local population structure provided by the geographically and ethnically representative sample in this study highlights the structured genetic landscape of Kenya.

How to prevent and address safeguarding concerns in global health research programmes: practice, process and positionality in marginalised spaces.

Safeguarding is rapidly rising up the international development agenda, yet literature on safeguarding in related research is limited. This paper shares processes and practice relating to safeguarding within an international research consortium (the ARISE hub, known as ARISE). ARISE aims to enhance accountability and improve the health and well-being of marginalised people living and working in informal urban spaces in low-income and middle-income countries (Bangladesh, India, Kenya and Sierra Leone). Our manuscript is divided into three key sections. We start by discussing the importance of safeguarding in global health research and consider how thinking about vulnerability as a relational concept (shaped by unequal power relations and structural violence) can help locate fluid and context specific safeguarding risks within broader social systems. We then discuss the different steps undertaken in ARISE to develop a shared approach to safeguarding: sharing institutional guidelines and practice; facilitating a participatory process to agree a working definition of safeguarding and joint understandings of vulnerabilities, risks and mitigation strategies and share experiences; developing action plans for safeguarding. This is followed by reflection on our key learnings including how safeguarding, ethics and health and safety concerns overlap; the challenges of referral and support for safeguarding concerns within frequently underserved informal urban spaces; and the importance of reflective practice and critical thinking about power, judgement and positionality and the ownership of the global narrative surrounding safeguarding. We finish by situating our learning within debates on decolonising science and argue for the importance of an iterative, ongoing learning journey that is critical, reflective and inclusive of vulnerable people.

Functional analysis of novel splicing and missense mutations identified in the ASS1 gene in classical citrullinemia patients.

BACKGROUND: Classical citrullinemia (CTLN1) is an inborn error of the urea cycle caused by reduced/abolished activity of argininosuccinate synthetase due to mutations in the ASS1 gene. To determine the pathogenicity of novel variants detected in patients is often a huge challenge in molecular diagnosis. The purpose of our study was to characterize novel ASS1 gene mutations identified in CTLN1 patients. METHODS: Exon trapping assay with pSPL3 was used to confirm splice aberrations while bioinformatics structural analysis predicted the possible effects of missense mutations. RESULTS: Novel donor site (c.174+1G>A) and missense (p.V141G) mutations were detected in a patient exhibiting a biochemical phenotype only. The splice mutation provoked exon skipping hence the truncated product. The mutation p.V141G, is predicted to disturb a hydrophobic pocket in the ATP binding domain in the ASS. Both mutations are predicted to lower binding of ATP. The second patient presented with early onset neonatal citrullinemia marked by an elevated biochemical profile and a clinical phenotype. Analysis revealed a donor site (c.773+1G>A) mutation leading to both exon skipping and intron retention. Subsequent introduction of premature stop codons would result in severely truncated products likely to be degraded. A previously reported R265C is predicted to distort the citrulline binding site. CONCLUSIONS: Three novel mutations are reported in this study. They expand the spectrum of genetic pathology underlying CTLN1. Overall this study provides new insight of CTLN1 and illustrates a comprehensive protocol investigating inborn errors of metabolism at the molecular level.