University of registration: University of Leicester
Non-Academic partner: Dr Martin Blythe - DNA Worldwide Group
Project title: Next-generation kinship deduction for forensic and genealogical analysis
The use of DNA analysis to determine familial relationships between human individuals is very well established. For close (first-degree) pairwise relationships as targeted in the paternity test, a small number of polymorphic markers (the short-tandem repeats [STRs] also used in forensic individual identification) is analysed, and probabilities of true paternity can be established with near certainty. However, there is also a need in some applications to estimate more distant kin relationships: in forensic casework ‘familial searching’ exploits the fact that a perpetrator and their relative(s) are expected to share ‘similar’ DNA profiles, which can provide investigative information when the relative(s) are in the National DNA Database but the perpetrator is not; in immigration cases a claim of relationship may need to be validated in order to allow entry to the UK; in genealogical research participants may have specific hypotheses about their relationships which they wish to support via DNA evidence. The kinship estimation problem is more difficult in these cases because with each additional generation that separates two individuals, the expected proportion of the genome shared identical by descent (IBD) halves. Additional power can be gained by increasing the number of DNA markers analysed, for example by using genome-wide SNP chips.
The project proposed here addresses these issues by exploring the potential of NGS forensic multiplexes and genome-wide SNP data in relationship estimation, using real-world data. Forensically relevant data will be generated by typing either the Promega Powerseq or Illumina Forenseq multiplex on existing pedigree DNA resources (e.g. CEPH families; French-Canadian deep-rooting pedigrees). Anonymised genome-wide SNP data will be obtained from DNA Worldwide (consenting clients, and a dataset of 72 individuals from 9 pedigrees). Both the forensic multiplexes and the genome-wide data (based on the HumanOmniExpressExome-8 chip) include uniparentally-inherited markers (Y chromosome, mitochondrial DNA) as well as biparentally-inherited (autosomal) markers. A novel feature of this project is to investigate efficient incorporation of such data with SNP-based likelihood estimates by considering haplotype frequencies and possible pedigree structures including sex. A key issue will be to understand the sensitivity of relationship estimation to allele frequencies, and a number of approaches will be taken, including the use of internal frequencies from the data themselves, data from public resources such as HapMap, or our own datasets. Consideration will also be given to population structure, admixture and the effects of linkage disequilibrium. Detailed sensitivity analyses will be carried out through extensive simulation studies.
Closing date for applications: 31st March 2017
iCASE students must fulfil the MIBTP entry requirements and will join the MIBTP cohort for the taught modules and masterclasses during the first term. iCASE students can then start their PhD project in Jan 2018 but must complete a 3-month miniproject (at a non-home institution) before the end of their first year. They will remain as an integral part of the MIBTP cohort and take part in the core networking activities and transferable skills training. MIBTP iCase.