Genomic DNA of three patients, born as healthy carriers and developing a late-onset severe transfusion-dependent beta-thalassemia major was studied by high density genome wide SNP array analysis. A... Show moreGenomic DNA of three patients, born as healthy carriers and developing a late-onset severe transfusion-dependent beta-thalassemia major was studied by high density genome wide SNP array analysis. A mosaic loss of heterozygosity for almost the entire 11p was found not attributable to deletions, but involving mosaicism for segmental paternal isodisomy of 11p. Mitotic recombination leading to mosaic segmental uniparental isodisomy on chromosome 11p in multiple tissues has been described as a molecular disease mechanism for a subset of sporadic Beckwith-Wiedemann syndrome cases. A similar mechanism also seems to be involved in causing late-onset disease in carriers of recessive mutations in other genes located in 11p, such as late-onset beta-thalassemia major and sickle cell disease. We suggest that the the loss of maternally imprinted IGF-2 and H19 genes may account for the selective advantage of hematopoietic cells containing this segmental paternal isodisomy of 11p carrying the beta-thalassemia mutation. Show less
Dieltjes, P.; Mieremet, R.; Zuniga, S.; Kraaijenbrink, T.; Pijpe, J.; Knijff, P. de 2011
Exploring technological limits is a common practice in forensic DNA research. Reliable genetic profiling based on only a few cells isolated from trace material retrieved from a crime scene is... Show moreExploring technological limits is a common practice in forensic DNA research. Reliable genetic profiling based on only a few cells isolated from trace material retrieved from a crime scene is nowadays more and more the rule rather than the exception. On many crime scenes, cartridges, bullets, and casings (jointly abbreviated as CBCs) are regularly found, and even after firing, these potentially carry trace amounts of biological material. Since 2003, the Forensic Laboratory for DNA Research is routinely involved in the forensic investigation of CBCs in the Netherlands. Reliable DNA profiles were frequently obtained from CBCs and used to match suspects, victims, or other crime scene-related DNA traces. In this paper, we describe the sensitive method developed by us to extract DNA from CBCs. Using PCR-based genotyping of autosomal short tandem repeats, we were able to obtain reliable and reproducible DNA profiles in 163 out of 616 criminal cases (26.5%) and in 283 out of 4,085 individual CBC items (6.9%) during the period January 2003-December 2009. We discuss practical aspects of the method and the sometimes unexpected effects of using cell lysis buffer on the subsequent investigation of striation patterns on CBCs. Show less
Lao, O.; Vallone, P.M.; Coble, M.D.; Diegoli, T.M.; Oven, M. van; Gaag, K.J. van der; ... ; Kayser, M. 2010
The current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with... Show moreThe current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with self-declared ancestry we have analyzed paternally, maternally and bi-parentally inherited DNA markers sensitive for indicating continental genetic ancestry in all four major U.S. American groups. We found that self-declared U.S. Hispanics and U.S. African Americans tend to show variable degrees of continental genetic admixture among the three genetic systems, with evidence for a marked sex-biased admixture history. Moreover, for these two groups we observed significant regional variation across the country in genetic admixture. In contrast, self-declared U.S. European and U.S. Asian Americans were genetically more homogeneous at the continental ancestry level. Two autosomal ancestry-sensitive markers located in skin pigmentation candidate genes showed significant differences in self-declared U.S. African Americans or U.S. European Americans, relative to their assumed parental populations from Africa or Europe. This provides genetic support for the importance of skin color in the complex process of ancestry identification. Show less
The general aim of the work described in this thesis is to help explain the variation in ageing by using the life history framework of B. anynana. Each chapter focuses on a different aspect of the... Show moreThe general aim of the work described in this thesis is to help explain the variation in ageing by using the life history framework of B. anynana. Each chapter focuses on a different aspect of the life history, together giving a complete picture of the origins of variation in ageing in this species. A central theme to every chapter is the relative influence of genes, the environment, and how they related to plasticity. A summarising discussion of all chapters, and a perspective on how the ideas in this thesis will contribute to ageing research in the future is also included. Show less
