Diana Hall received her PhD in Forensic Genetics from the Catholic University of Rome for her research on background linkage disequilibrium across human populations, carried out at the Department of Human Genetics of the University of Chicago. She continued her postdoctoral studies on disease mapping of complex traits at the Rockefeller University of New York. Since 2010, Diana Hall is responsible of research at the Forensic Genetics Unit of the University Hospital of Lausanne-Geneva. Diana’s current research projects focus on novel molecular approaches for DNA mixture analyses. Her research includes the study of novel genetic markers for forensic casework, non-invasive prenatal paternity testing, individual ancestry inference and solid organ transplant monitoring.
Study and resolution of unbalanced DNA mixtures
The success of DNA profiling depends on the ability to obtain interpretable DNA profiles. Many traces contain cells and, hence, DNA, from more than a single individual, giving rise to mixed genotypes and difficulties in interpreting the results. An even more challenging situation occurs in the analysis of traces in which the cells of a victim are much more abundant than the cells of the perpetrator. Because of PCR amplification bias, the genetic identification of a DNA that contributes trace amounts to a mixed sample represents a tremendous challenge. This means that standard genetic markers, namely microsatellites, also referred to as Short Tandem Repeats (STR), and Single Nucleotide Polymorphism (SNP) have limited power in addressing common questions of forensic and medical genetics. To address this issue, we developed a molecular marker, named DIP-STR that relies on pairing deletion/insertion polymorphisms (DIP) with STR. The multiallelic haplotype composed of both DIP and STR alleles is analyzed by using PCR primers overlapping the deleted/inserted sequence on one side and downstream the STR region on the other side. This novel analytical approach allows for the unambiguous genotyping of a minor component in the presence of a major component, where DIP-STR genotypes of the minor were successfully procured at ratios up to 1:1000. The compound nature of this marker generates a high level of polymorphism that is suitable for identity testing.
Prenatal paternity tests and solid organ transplant monitoring
Samples containing highly unbalanced DNA mixtures from two individuals also occur in vivo during pregnancy or following organ transplant.Sex crime victims are sometimes unclear whether the father of their unborn child is the attacker or their loving partner.To identify the biological father, it is in principle possible to use the small quantities of cell free DNA of the fetus (cffDNA) that circulate in the maternal blood. With the use of DIP-STR markers we are currently studying the features of maternal DNA microchimerism during pregnancy and the possibility for an early paternity test. Similarly, we are investigating if correlations exist between DNA microchimerism (presence and quantity) in kidney transplant recipients and the clinical profile of the patient (e.g. rejection vs. tolerance) evaluated in both cross-sectional and longitudinal studies. The quantitative analysis of such correlations aims at establishing new and more informative peripherals biomarkers of organ transplant monitoring.
Individual ancestry inference
A second major limitation of conventional forensic genetic markers is their lack of association with any determinants of genetic disease or physical traits. This means that today’s DNA tests do neither provide any private information, nor indications about the general appearance of the person that could be used to guide investigations.To tackle this problem, we exploit the haplotype nature of DIP-STR markers. Briefly, the combination of two polymorphisms (DIP and STR) with different mutation rates makes these markers suitable for predicting the ancestry of a DNA source to be used as investigative lead.To assess the power of DIP-STR markers in assigning individuals to specific demographic group we carried out a worldwide population survey using the most widely used reference population from the Human Genome Diversity CEPH panel (HGDP-CEPH). The HGDP-CEPH sample set contains 1,064 individuals from 52 populations throughout the 5 continents that are: African, European, North African/Middle Eastern, Central-South Asian, East Asian, Native American and Oceanian populations.This study will allow us to measure the relative value of our markers with respect to other validated AIM marker sets.
Oldoni F, Castella V, Hall D. Application of DIP-STRs to sexual/physical assault investigations: Eight case reports. Forensic Science International: Genetics 30:106-13 (2017)
OldoniF, CastellaV, GrosjeanF, HallD. Sensitive DIP-STR markers for the analysis of unbalanced mixtures from “touch” DNA samples. Forensic Science International: Genetics 28:111-7 (2017)
Oldoni F, Castella V, Hall D. A novel set of DIP-STR markers for improved analysis of challenging DNA mixtures. Forensic Science International: Genetics 19:156-64 (2015)
Castella V, Gervaix J, Hall D. DIP-STR: highly sensitive markers for the analysis of unbalanced genomic mixtures. Human Mutation 34:644-54 (2013)