Southeast Asian Ovalocytosis (SAO) is an autosomal dominantly inherited, classically asymptomatic condition, that is widespread in Southeast Asian populations of Malasia, Indonesia, Papua New Guinea and the Philippines. Some regions have close to 30% prevalence and this is thought to be due to SAO providing partial protection against malaria. SAO is characterized by rigid, spoonshaped, ovalocytic red blood cells. The underlying defect is a deletion of 27bp in the band 3 gene, resulting in the absence of 9 amino acids (400-408) at the boundary of the cytoplasmic and membrane domains of band 3, causing abnormal structure and function. SAO is tightly linked in all cases to the band 3 Memphis 1 polymorphism, which is a lysine 56 (AAG) –glutamic acid (GAG) substitution. This polymorphism can be inherited independently and the prevalence ranges from about 6-30% according to various populations studied. The presence of SAO in a Cape Coloured family is a recent finding. The purpose of this study was to further investigate the prevalence of SAO and the band 3 Memphis 1 polymorphism in the Cape Coloured population. 20 unrelated individuals with SAO morphology were identified. DNA analysis revealed the 27bp deletion of exon 11 of the band 3 gene in all 20 subjects, which is diagnostic of SAO. This indicates a high occurrence of the SAO mutation in the Cape Coloured population, which is speculated to be due to a founder effect. Some of the clinical features differed from classically described SAO as some individuals showed evidence of haemolysis. Protein analysis showed all 20 individuals to have a reduced band 3 mobility, indicating the band 3 Memphis 1 polymorphism. Detecting the band 3 Memphis 1 polymorphism on a protein level is time consuming and labour intensive, therefore a PCR assay, which utilizes DNA, was developed for the rapid screening of this polymorphism. The PCR assay was based on a nucleotide mismatch which created a Taq 1 restriction site when combined with the band 3 Memphis 1 allele, but not with the wild type allele. Digestion of the PCR product with Taq 1 allowed differentiation between the two alleles. It was established that the band 3 Memphis 1 polymorphism has a high prevalence in the Cape Coloured population as it was detected in 108/326 (33%) of the individuals studied. Analysis indicated the Memphis allele is in Hardy-Weinberg equilibrium. / Prof. T.L. Coetzer Dr. H. Abrahamse

This thesis details the development of two computational tools, Telomerecat and Parabam, as well as their applications to whole genome sequencing (WGS) data. Telomerecat is a tool for estimating telomere length from WGS data. The strength of Telomerecat lies in its applicability. This applicability is due to a number of advantages over previous attempts to estimate telomere length from WGS. Chief amongst these advantages is that it makes no assumption about the underlying chromosome count or size of the genome within input samples. This means that Telomerecat lends itself well to analysing cancer samples where such assumptions are unfounded. This also means it is applicable to non-human samples, a first for tools of its kind. Furthermore, a novel method for filtering reads derived from interstitial telomere sequences means that it does not rely on previously applied analyses, a source of bias. The other tool described in this thesis is Parabam. Parabam is the first tool of its kind to allow users to apply a function to all of the reads in sequence alignment files, in parallel. Furthermore, Parabam includes a novel method for iterating over index sorted sequence files as if they were name sorted. We provide evidence that Parabam is a quicker way to create complex subsets and statistics from sequence alignment files. In the latter half of the thesis we detail two applications of Telomerecat to large scale WGS projects. The first application, to the Prostate ICGC UK cohort, unveils hitherto uncovered associations between telomere length and previously identified molecular subtypes as well as cancer stage. In the second application, to the NIHR BioResource - Rare Disease cohort, we discover a previously unidentified variant in DKC1 that we propose is directly linked to short telomeres and an immunodeficient phenotype.

Bakgrund Sjuksköterskans roll i vårdandet av patienter med maligna blodsjukdomar är utmanande då sjuksköterskan ska stötta patienten genom både diagnos och behandling. Personcentrerad omvårdnad gör att patienten lär sig om sjukdomen och blir delaktig i behandlingen. Syfte Syftet är att beskriva sjuksköterskors erfarenheter av att vårda vuxna patienter med maligna blodsjukdomar. Metod Arbetet utformades som en strukturerad litteraturöversikt med inslag av metodologi som används vid systematiska litteraturstudier, med fokus på sjuksköterskors erfarenheter. Databaserna CINAHL och PubMed användes och sju artiklar publicerade 2013–2023 sammanställdes. Resultat Sjuksköterskornas erfarenheter av att vårda patienter med maligna blodsjukdomar belystes via kategorierna Kommunikation och Utmaningar för sjuksköterskor samt underkategorierna Kommunikation mellan sjuksköterskor och patienter, Kommunikationinom vårdteamet, Emotionell påverkan, Överlevnadsvård och Palliativ vård vid maligna blodsjukdomar. Slutsats Sjuksköterskorna upplevde kommunikation som viktig del i vårdandet av patienter med maligna blodsjukdomar i relation mellan sjuksköterskor-patienter samt sjuksköterskor vårdteamet. Sjuksköterskorna upplevde även att det var lätt att bli emotionellt påverkad i arbetet. Hantering och utförande av överlevande- och palliativ vård var en utmaning för sjuksköterskorna som arbetade med patienter som har diagnostiserats med maligna blodsjukdomar. / Background Nurse's role in caring for patients with malignant blood disorders is challenging. Nurses must support the patient through a diagnosis and the course of treatment. Person-centred care means that the patient learns about the disease and becomes involved in thetreatment. Aim The aim is to describe nurses` experiences of caring for adult patients with malignant blood diseases. Method This review was made with a methodology similar to ones used in systematic reviews with a focus on nurses` experience. The databases CINAHL and PubMed were used. Seven articles were found. The included articles in the results were published between 2013–2023. Results Nurses' experiences of caring for patients with malignant blood diseases were highlighted by the categories Communication and Challenges for nurses and the subcategories Communication between nurses and patients, Communication within the care team, Emotional impact, Survival care and Palliative care for malignant blood diseases. Conclusions Nurses experienced communication as an important part in the care of patients with malignant blood diseases in the relationship between nurses-patients and the nurses-care team. Nurses also felt that it was easy to be emotionally affected at work. Management and delivery of survivorship and palliative care was a challenge for nurses working with patients diagnosed with blood malignancies.

Humant immunbristvirus (HIV), hepatit B och C är blodsmittor som finns världen över. Dessa tre sjukdomar anses som allmänfarliga och som anmälningspliktiga sjukdomar. Livet med en smittsam blodsjukdom kan vara påfrestande för en patient, både fysiskt och psykiskt. Syftet med denna litteraturstudie var att beskriva patienters upplevelse av att leva med en smittsam blodsjukdom. Studien är en allmän litteraturstudie, där kvalitativ forskning användes för att få fram resultatet. Resultatet består av tre teman och sju subteman. De teman som skapades var: rädsla, känslan av att vara osedd och känslan av att vara sedd. Livet med en smittsam blodsjukdom kan vara påfrestande för en patient. Rädslan för sjukdomens konsekvenser är stor. Socialt stöd från anhöriga och sin omgivning har stor påverkan på patientens liv. Brist på socialt stöd kan bidra till att patienten drar sig undan, tar till alternativa hjälpmedel såsom alkohol och narkotika samt till att patienten utvecklar depression. Som vårdpersonal är det viktigt att se patienten bakom den smittsamma blodsjukdomen, då patienter ibland upplever mötet med sjukvården som något negativt. Vårdpersonalen som är rädda för sjukdomen, är även rädda för att bli smittade. Det bidrar till att patienten känner sig dömd och väljer att avstå från behandlingar. / Human immunodeficiency virus (HIV), hepatitis b and c are contagious blood diseases that exists worldwide. These three diseases are considered to be generally dangerous and as a notifiable disease. Living with a contagious blood disease can be stressful to patients both physically and mentally. The purpose of this literature study was to describe patients' experience of living with contagious blood diseases. The study is a general literature study, where qualitative research was used to produce the result. The result consists of three themes and seven different subthemes. That resulted in the creation of three themes: fear, the feeling of being unseen and the feeling of being seen. Living with a contagious blood disease can be stressful to a patient. There is a great fear for the consequence of the disease. Getting social support from relatives and their social environment has a major impact on the patient's life. The lack of social support can make the patient avoid social contact. Patients’ take alternative means such as alcohol, drugs and the patient can develop depression. As a formal caregiver it is important to see the person behind the infection, as the patient experience the meeting with formal caregivers as negative. The formal caregivers are afraid of the disease and to be infected. The patient feels judged and chooses to avoid treatment.