Sex chromosomes are useful in elucidating the evolutionary factors affecting diversity and divergence. In particular, Y chromosome analyses may complement studies using mitochondrial DNA for inferring sex-specific population genetic processes. Y chromosome studies have been scarce due to limited access to genetic markers and the dynamic evolution of Y. Conserved Y-specific primers that could amplify a diverse set of mammalian species were developed from comparison of gametologous X and Y sequences. Y-specific sequence, generally more than one kb, was amplified for all 20 species examined. Intraspecific diversity on mammalian Y was found to be reduced even when male-biased mutation rate and effective population size were corrected for. A number of factors can cause this low variation on Y of which selection on a haploid chromosome seems most important. The field vole (Microtus agrestis), a common and well-studied small mammal in Eurasia, was examined for X and Y variability. Earlier studies on mtDNA had shown that the field vole is separated in two distinct lineages in Europe. The X and Y chromosome sequences confirmed the deep split and suggested that the two lineages of field vole should be reclassified as two separate species. Two distinct Y chromosome haplogroups were found in modern European cattle, distributed among breeds according to a north-south gradient. Ancient DNA analysis of European aurochsen showed the northern haplogroup to be the most common, possibly indicating local hybridization between domestic cows and wild aurochs bulls in Europe.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases affecting 0.05-2% of the population worldwide. Genetic studies detected linkage with SLE in the 2q37 region, and intensive family-based and case-control association studies in several populations identified that allele A of the SNP PD-1.3 located in the immunoreceptor PDCD1 (PD-1) gene, increases risk of the disease by 2.6-fold in Caucasians (p<0.00001) and by 3.5-fold in Mexicans (p=0.0009). The same allele was found to be a risk factor for lupus nephritis, a severe clinical manifestation of SLE. In Swedish and European-American females with SLE, patients with the allele A had nephritis 1.8 times (p=0.01) more often than patients with allele G . Moreover, the allele A was also found 1.8 times (p=0.005) more often in RA patients, negative for the known risk-factors, rheumatoid factor and the shared epitope, than in other groups of patients and controls. Functional studies demonstrated that the mechanism behind the SNP PD-1.3 is related to the disruption of the binding site for RUNX transcription factors in the regulatory region. Expression of the PD-1 and RUNX genes was altered in the activated T cells of SLE patients compared to controls. The Tumor Necrosis Factor Receptor 2 (TNFR 2) gene was studied as a second candidate gene for both SLE and RA. The results of our studies in SLE and RA patients and controls from Sweden and Mexico do not support the association of the polymorphism TNFR 2 M196R with these diseases. Other polymorphisms in this gene and other genes in this region should therefore be studied.

Glaucoma is one of the leading causes of visual impairment in the world. In glaucoma, the patient’s peripheral vision is lost due to progressive and irreversible deterioration of the retinal ganglion cells and atrophy of the optic nerve. The effect on the visual field is gradual and painless, and the progression so slow, that the patient may not notice until a substantial part of the visual field is lost. If left untreated, glaucoma can lead to blindness. In this thesis, genes associated to glaucoma have been analysed in Swedish patients with primary open angle and exfoliative glaucoma. The genes studied were MYOC, oculomedin, GSTM1 and OPTN. The coding sequence of MYOC was analysed and mutations were found in 1% of the primary open angle glaucoma patients. Additionally, a predisposing variant was found in 1% of the patients as well as in 0.5% of the controls. No disease-associated variation was found in the exfoliative glaucoma cases. Mutations were also found in two families affected by glaucoma. The coding sequence of oculomedin was analysed, but none of the variants found were classified as disease causing in either patient group. GSTM1 was analysed for its presence in the patients. No association could be found for either hetero- or homozygous deletions. The coding sequence and haplotype distribution of OPTN was analysed. None of the variants found were classified as disease causing and none of the haplotypes were associated to the disease in either patient group. There are just a few per cent of the Swedish primary open angle glaucoma patients with genetic variation associated to disease, in the genes analysed in this study. No association to exfoliative glaucoma was found. This indicates heterogeneity in the genetics of glaucoma when different subtypes and different populations are compared. Likely, there are genes still to be identified.

Recent studies have shown that the somatic mutation status of the immunoglobulin (Ig) VH genes can divide chronic lymphocytic leukemia (CLL) into two prognostic subsets, since cases with mutated VH genes display superior survival compared to unmutated cases. Biased VH gene usage has also been reported in CLL which may reflect antigen selection. We performed VH gene analysis in 265 CLL cases and confirmed the prognostic impact of the VH mutation status. Preferential VH gene usage was also demonstrated in both the mutated and unmutated subset. Interestingly, CLL cases rearranging one particular VH gene, VH3-21, displayed poor outcome despite that two-thirds showed mutated VH genes. Many of the VH3-21 cases expressed λ light chains, rearranged a Vλ2-14 gene, and had homologous complementarity determining region 3s (CDR3s), implying recognition of a common antigen epitope. We believe that the VH3-21 subset comprises an additional CLL entity. To further explore the B-cell receptors in CLL, we analyzed the VH gene rearrangements and, specifically, the heavy chain CDR3 sequences in 346 CLL cases. We identified six new subgroups with similar HCDR3 features and restricted VL gene usage as in the VH3-21-using group. Our data indicate a limited number of antigen recognition sites in these subgroups and give further evidence for antigen selection in the development of CLL. Different cutoffs have been suggested to distinguish mutated CLL in addition to the 2% cutoff. Using three levels of somatic mutations, i.e. <2%, 2-5% and >5%, we divided 323 CLLs into subsets with divergent survival. This division revealed a low-mutated subgroup (2-5%) with inferior outcome that would have been masked using the traditional 2% cutoff. A 1513A/C polymorphism in the P2X7 receptor gene was reported to be more frequent in CLL, but no difference in genotype frequencies was revealed in our 170 CLL cases and 200 controls. However, CLL cases with the 1513AC genotype showed superior survival than 1513AA cases and this was in particular confined to CLL with mutated VH genes. In summary, we could define new prognostic subgroups in CLL using Ig gene rearrangement analysis. This also allowed us to gain insights in the biology and potential role of antigen involvement in the pathogenesis of CLL.

The aim of this thesis is to explore why parents bring their children to homeopaths and to investigate the effect of homeopathic treatment for prevention of upper respiratory tract infections (URTI) in children. The reason for doing studies on this is that there has been a nearly threefold increase in the proportion of children among patients visiting Norwegian homeopaths. This raised the question of why it is so. Furthermore, recurrent respiratory complaints are a main reason why child patients consult homeopaths. This raised the question of the effect of homeopathic treatment in this patient group, because there is very little research on this. The thesis builds on four different studies conducted between August 2002 and June 2004. Parents of nine children that recently had been to a homeopath for the first time were interviewed to explore why parents take their children to homeopaths. All parents had been to a medical doctor before consulting the homeopath. It was the experiences with conventional medical treatment that led the parents to look for alternatives. The reasons were that 1) the parents did not want to give the medication prescribed by the doctor, 2) they wanted treatment while waiting for a problem to be assessed, 3) they did not want to continue to use the prescribed medication, 4) they stopped taking conventional medication due to side effects or 5) they were not offered any treatment by the medical doctor. The parents would consult a medical doctor if they felt insecure about the health conditions of the child and would visit a homeopath when they felt that the situation was clarified. There are parents who take their child to homeopaths despite not understanding or having belief in whether ultramolecular homeopathic medicines can have effects. One hundred and sixty-one children who had been diagnosed with an URTI by a medical doctor were recruited to participate in a trial on the effect of treatment by homeopaths for prevention of URTI in children. The children were randomly allocated to two groups. One group received an appointment immediately with one of five homeopaths who treated the patients as they do in their everyday practice. The other group (control) got such treatment after three months. The occurrence of URTI judged by the parents were significantly lower among those treated immediately by homeopaths (median 8 days in three months) compared to the control group who used self-selected conventional health care (median 13 days) (p=0.006). Homeopathic medicines are frequently used for self-treatment (over the counter-OTC). It is not known if the choice of the patient is the same, as a homeopath would have prescribed. A study was therefore conducted to explore if there can be developed indications for homeopathic medicines that facilitate that parents can chose the same medicine as a homeopath would prescribe for children with URTI. Firstly, data from a survey was used to find three medicines Calcarea carb, Pulsatilla and Sulphur that accounted for 60% of all prescription made by Norwegian homeopaths for children with URTI. Simplified constitutional indications for these medicines were developed and tested by comparing the choices of 70 parents with the prescription of eleven homeopaths. The parents were able to choose the same homeopathic medicine as homeopaths prescribed for 55% of the children. Two hundred and fifty-nine children who had been diagnosed with an URTI by a medical doctor were recruited to participate in a trial on the effect of one of three self-selected ultramolecular homeopathic medicines for prevention of URTI in children. The indications developed were used. The children was randomly allocated to receive either ultramolecular homeopathic medicine (C-30) or placebo. There was no difference in the occurrence of URTI judged by the parents among getting ultramolecular homeopathic medicine compared to those getting placebo (median 9 days in three months for both groups) (p=0.531). / Hensikten med denne avhandlingen er å undersøke hvorfor foreldre tar sine barn med til homøopat og å undersøke effekten av homøopatisk behandling i forebygging av øvre luftveisinfeksjoner (ØLI) hos barn. Bakgrunnen for de undersøkelsene som er gjort, er at det nesten er en tredobling i andelen barn blant pasienter hos homøopat. Dette utløste spørsmål om hvorfor det er slik. Videre er gjentatte luftveisplager en hovedårsak til at barn oppsøker homøopat. Fordi det er lite forskning på dette temaet ble spørsmålet om effekten av homøopatisk behandling i denne pasientgruppen også utløst. Avhandlingen bygger på fire ulike undersøkelser som er gjennomført mellom august 2002 og juni 2004. Foreldre til ni barn som nylig hadde vært hos homøopat for første gang ble intervjuet for å undersøke hvorfor foreldre tar sine barn med til homøopat. Alle foreldrene hadde vært hos lege før de kontaktet homøopaten, og det var erfaringer med legebehandlingen som fikk foreldrene til å søke alternativer. Årsakene var at foreldrene 1) ikke ønsket å gi den behandlingen lege foreskrev til barnet, 2) ønsket behandling mens barnet ventet på å bli ferdig utredet, 3) ønsket å avslutte bruken av de medisinene legen hadde foreskrevet for barnet, 4) opplevde at barnet fikk bivirkninger av behandlingen legen hadde gitt og 5) ikke ble tilbudt noen behandling hos legen. Foreldre oppsøker først lege når de er usikre eller bekymret for barnets helsetilstand. De oppsøker homøopat for behandling når dette er avklart. Det er foreldre som oppsøker homøopat med sine barn selv om de ikke forstår eller tror på effekten av homøopatiske medisiner (som kan være svært fortynnet). Ett hundre og sekstini barn som hadde vært til lege på grunn av en øvre luftveisinfeksjon ble rekruttert til å være med på en undersøkelse av effekten av behandling hos homøopat i forebyggingen av ØLI hos barn. Barna ble tilfeldig fordelt i to grupper. Barna i den ene gruppen fikk time med en gang hos en av fem homøopater som foreskrev homøopatisk behandling på vanlig måte. Den andre gruppen fikk slik behandling etter 3 måneder. Forekomsten av ØLI Hensikten med denne avhandlingen er å undersøke hvorfor foreldre tar sine barn med til homøopat og å undersøke effekten av homøopatisk behandling i forebygging av øvre luftveisinfeksjoner (ØLI) hos barn. Bakgrunnen for de undersøkelsene som er gjort, er at det nesten er en tredobling i andelen barn blant pasienter hos homøopat. Dette utløste spørsmål om hvorfor det er slik. Videre er gjentatte luftveisplager en hovedårsak til at barn oppsøker homøopat. Fordi det er lite forskning på dette temaet ble spørsmålet om effekten av homøopatisk behandling i denne pasientgruppen også utløst. Avhandlingen bygger på fire ulike undersøkelser som er gjennomført mellom august 2002 og juni 2004. Foreldre til ni barn som nylig hadde vært hos homøopat for første gang ble intervjuet for å undersøke hvorfor foreldre tar sine barn med til homøopat. Alle foreldrene hadde vært hos lege før de kontaktet homøopaten, og det var erfaringer med legebehandlingen som fikk foreldrene til å søke alternativer. Årsakene var at foreldrene 1) ikke ønsket å gi den behandlingen lege foreskrev til barnet, 2) ønsket behandling mens barnet ventet på å bli ferdig utredet, 3) ønsket å avslutte bruken av de medisinene legen hadde foreskrevet for barnet, 4) opplevde at barnet fikk bivirkninger av behandlingen legen hadde gitt og 5) ikke ble tilbudt noen behandling hos legen. Foreldre oppsøker først lege når de er usikre eller bekymret for barnets helsetilstand. De oppsøker homøopat for behandling når dette er avklart. Det er foreldre som oppsøker homøopat med sine barn selv om de ikke forstår eller tror på effekten av homøopatiske medisiner (som kan være svært fortynnet). Ett hundre og sekstini barn som hadde vært til lege på grunn av en øvre luftveisinfeksjon ble rekruttert til å være med på en undersøkelse av effekten av behandling hos homøopat i forebyggingen av ØLI hos barn. Barna ble tilfeldig fordelt i to grupper. Barna i den ene gruppen fikk time med en gang hos en av fem homøopater som foreskrev homøopatisk behandling på vanlig måte. Den andre gruppen fikk slik behandling etter 3 måneder. Forekomsten av ØLI var signifikant lavere hos de som fikk behandling hos homøopat med én gang (median 8 dager på tre måneder) sammenlignet med den andre gruppen som brukte standard behandling ved behov mens de ventet (median 13 dager) (p=0,006). Homøopatisk medisin brukes internasjonalt i stor grad til selvbehandling. Man vet ikke om pasientens eget valg av homøopatisk medisin er lik det en homøopat ville foreskrevet. Det ble derfor gjennomført en undersøkelse av om det kan utvikles beskrivelser for indikasjoner for homøopatiske medisiner som gjør at foreldre kan velge samme medisin som en homøopat foreskriver for barn med ØLI. Først ble det funnet fram til tre medisiner, Calcarea carb, Pulsatilla og Sulphur som homøopater i Norge foreskriver til 60% av barn med ØLI. Så ble det utviklet indikasjoner for disse tre medisinene som ble testet ut ved at valgene til 70 foreldre ble sammenlignet med foreskrivingen til 11 homøopater. Foreldrene valgte samme medisin som homøopaten for 55% av barna. To hundre og femtien barn som hadde vært til lege på grunn av en øvre luftveisinfeksjon ble rekruttert til å være med på en undersøkelse av effekten av en av tre selvvalgte homøopatiske medisiner i forebyggingen av ØLI hos barn. Indikasjonene som ble utviklet ble brukt. Barna ble tilfeldig fordelt til enten å få homøopatisk medisin eller placebo. Det var ingen signifikant forskjell i forekomsten av ØLI mellom de som fikk homøopatisk medisin sammenlignet med de som fikk placebo (median 9 dager på tre måneder i begge grupper) (p=0,531).

Positional cloning is a method to identify genes from their position in the genome without prior knowledge about function. We used this approach to investigate the basis for three distinct genetic disorders; Obesity, Ichthyosis Prematurity Syndrome and Meniere's disease. Obesity appears when energy intake exceeds energy expenditure which leads to an abnormal accumulation of fat in the adipocyte tissue. We have studied a family with a balanced chromosomal translocation t(4;15) segregating with severe obesity. The chromosomal breakpoints create a fusion gene involving the gene for isoform 1 of RAR-related orphan receptor A (RORa1) which is implicated in the regulation of adipogenesis and lipoprotein metabolism. We hypothesize that the obesity in this family is caused by haploinsufficiency of this gene or a gain of function of the fusion gene. Ichthyosis prematurity syndrome (IPS) is a rare skin disorder belonging to a group of autosomal recessive congenital ichthyosis. We have mapped the locus for IPS to chromosome 9q34. Within the IPS locus, we identified a core haplotype with a high carrier frequency among affected, which indicate a possible founder mutation for the disease. The minimal shared region in affected patients contains seven genes which are candidates for IPS. Meniere's disease (MD) is characterised by spontaneous attacks of vertigo, fluctuating sensorineural low frequency hearing loss, aural fullness, and tinnitus. We mapped the MD locus to chromosome 12p13 using three Swedish families. The linked region is 463 kb, containing only one gene, a phosphoinositide-3-kinase (PIK3C2G). Involvement of phosphatidylinositol 3-kinases (PI-3K) in the intra cellular signalling cascades of cells in mammalian balance epithelia makes this gene a good candidate gene for MD.

<p><strong>Inledning:</strong> När en äldre människa har ett stort omvårdnadsbehov finns möjligheten att flytta till ett särskilt boende. Då äldres vardag ser olika ut är det av yttersta vikt att omvårdnadspersonalen kan ge stöd och hjälp så att den äldre skall kunna anpassa sig till den nya situationen. <strong>Syfte:</strong> Syftet med denna studie är att belysa hur anhöriga upplever att deras närstående i särskilt boende får en god omvårdnad. Metod: En kvalitativ ansats med empiriskt inslag användes där anhörigas upplevelser av omvårdnad, delaktighet och bemötande insamlades med hjälp av intervjuer. <strong>Resultat:</strong> Tre olika kategorier Omvårdnad, Delaktighet och Bemötande med nio underkategorier. En betydelsefull del i omvårdnaden är att det skapas en god kontakt mellan anhöriga och omvårdnadspersonalen för att finna ett bra sätt att kommunicera på. Det framkom hur viktigt det är att som vårdtagare känna att de blir sedda för den de är och att de får vara delaktiga i de omvårdnadsåtgärder som beslutas av omvårdnadspersonalen. <strong>Diskussion: </strong>Resultatet kan bidra till en ökad förståelse för anhörigas upplevelser av hur omvårdnaden bedrivs i särskilt boende. När anhöriga göras mer delaktiga i omvårdnaden, kan det leda till en bättre omvårdnad för vårdtagaren i särskilt boende. <strong>Slutsats:</strong> Resultatet som författarna kom fram till skulle kunna användas i utbildningssyfte då omsorgen av äldre människor kräver att omvårdnadspersonalen ständigt förnyar sina kunskaper. Detta kan vara till gagn för sjuksköterskan, de anhöriga och de äldre som bor i särskilt boende.</p> / <p><strong>Introduction:</strong> When a senior person has a large need for special care there is an option to relocate to a nursing home. The seniors every day varies there for it is of outmost importance the nursing care staff can support the senior that he maybe adapt to the new situation. <strong>Purpose:</strong> The purpose with this study is to enlighten how relatives experience their close ones in special nursing home receive good care treatment. Method: A quality approach with empirical elements is used where relatives experiences of care, being part of and recievment was collected with the help of interviews. <strong>Results:</strong> Three categories Care, Involvment and Recievment with nine sub categories. An important part in care is to create good contact between relatives and nursing care staff to evolve good ways for communication. It was revealed how important it is as a health care patient to feel they’re being looked upon for who they are and they be part of treatment measures and decisions made by nursing care staff. <strong>Discussion:</strong> The results can contribute to an increased understanding to how relatives experience care is being conducted in a special accommodation. When relatives are made more involved in care, may lead to a better care for care patient in a nursing home. <strong>Conclusion:</strong> The results which have been concluded could be used in educational purposes when the care of senior people demands that nursing care staff continuously renews their knowledges. This could be of use for the nurse, the relatives and the seniors living in a nursing home.</p>

Heritable ossification defects of the skull vault often present as enlarged parietal foramina (PFM), bilateral oval openings of the posterior parietal bones. Isolated PFM may originate from wider defects in infancy and usually show an autosomal dominant mode of transmission, offering unexplored genetic insights into the molecular pathways of calvarial development. Haploinsufficiency of the homeobox gene MSX2, located at 5q34-q35, underlies a fraction of PFM families but the locus can be excluded in others, indicating heterogeneity. The proximal 11p deletion syndrome (P11pDS), characterised by multiple exostoses (due to haploinsufficiency of EXT2), occasional mental retardation, and PFM, pointed to a second locus at 11p11-p12. The human orthologue of the mouse paired-like homeobox gene Alx4 was identified adjacent to EXT2. ALX4 was structurally characterised and heterozygous loss-of-function mutations were detected in association with skull vault defects in twenty-nine individuals from six families, including a new case of P11pDS. The calvarial phenotype of ALX4 mutations was almost indistinguishable from the MSX2-caused defects and ranged from a midline gap to non-penetrance, nevertheless typified by classical PFM; abnormal morphology of the dural septa was also observed. The mutation spectrum and the subtle genotype-phenotype correlations suggested haploinsufficiency as the predominant pathophysiological mechanism. Interestingly, Alx4^-/+ mice manifest polydactyly but no skull defects, illustrating species-specific dosage sensitivity. Two new MSX2 mutations were also ascertained, one of which segregated with PFM and clavicular hypoplasia. The potential contribution of ALX4 and MSX2 to premature fusion of the cranial sutures - craniosynostosis - was investigated, but no unequivocally pathogenic variants were found. To elucidate the functions of Alx4 and Msx2 in skull development, spatial expression analysis was performed in mouse embryos between embryonic days E12.5-E17. Transcripts of both Alx4 and Msx2 were seen in the early calvarial skeletogenic condensations and in later stages their expression displayed a more restricted pattern, overlapping minimally with the domains of mature bone. By assessing expression in embryonic heads of reciprocal knockout mice, activation of Alx4 was found to be independent of functional Msx2 and vice versa. Analysis of compound mutants demonstrated that the two loci exert roughly additive effects on the skull vault while protein interaction assays did not indicate any physiological interaction between Alx4 and Msx2. Hence, Alx4 and Msx2 appear to regulate proliferation, differentiation, or survival of osteoblast precursors and pre-osteoblasts through parallel pathways.

With transformative initiatives like the UK's 100,000 Genomes Project underway, vast amounts of data from genome sequencing are being generated. Genomic results are being actively returned to participants, although policies around their management remain inconsistent and a subject of debate. Secondary findings (SF) have been of particular concern - variants associated with health conditions other than the indication for sequencing, which may or may not be medically actionable. I have conducted a mixed methods study to explore the current transitional period and the issue of secondary findings, and inform future management. Following a narrative review of the literature around SF in genome sequencing and a focused systematic review of primary studies on stakeholder views towards the subject (Part I), gaps in the current literature were identified. These were, chiefly: (1) the need for diverse stakeholder views based on experience making actual decisions around SF; and, (2) empirical data - phenotypic, psychological, behavioural - on actual returned SF. Thus, taking advantage of the local programme of translational genome sequencing, I conducted qualitative studies involving genomic healthcare professionals and genome sequencing participants, to explore their views towards genomic medicine and SF (Part II). Following this, I detail a case study illustrating the process and challenges of returning an SF, as well as outline a study designed to collect empirical data on actual returned SF and present preliminary data to this end (Part III). I illustrate that secondary findings will be a part of tomorrow's genomic medicine: cautious optional screening of actionable SF (including treatable conditions and carrier status information) appears favourable. However, if SF are to be a part of the genomic medicine paradigm, several barriers must be considered: insufficient connectivity between specialties, variant interpretation, clinical interpretation and management, and overpromise and expectations (including recontact in light of new information). In order to overcome these challenges, individuals in unselected populations must be prospectively phenotyped to derive more accurate estimates of population-level penetrance and better understand the full phenotypic spectrum, and we must explore the downstream impact of disclosure. As genome sequencing is mainstreamed, clear evidence-based guidelines for SF in genome sequencing will be essential if harms are to be minimised and benefits are to be maximised, both for participants and the healthcare system at large. At this point, albeit cautiously, we must 'learn by doing'.

Genetic and functional studies have demonstrated that KIR gene polymorphism, including different haplotypes, allelic polymorphisms and different expression levels of KIRs, may all play a part in the association with HIV-1 infection outcome. Currently, there are very few studies focusing on the association between KIR and HIV in the Chinese population. In this project, we started to look at the polymorphism of KIRs in a unique chronic HIV-1 infected cohort (SM cohort), evaluating the impact of KIR and KIR-HLA interactions in terms of HIV-1 infection progression. The SM cohort is unique because the major factors such as viral strain, transmission route and timing of infection, which could affect the natural history of HIV-1, have been narrowly controlled. Through comparison with a healthy control population, some genetic associations were identified. The frequency of KIR2DL3 was lower in the “slow progressors” group; the compound genotype of KIR3DS1+ Bw4 homozygotes was significantly lower in the “slow progressors” group; additionally, group B genotypes (multiple activating genes) were shown to be likely to mount a greater immune pressure on HIV-1. In terms of KIR footprints, several amino acid positions were identified for which the substitution of an amino acid may be ascribed to the immune response from KIR-modulated NK cells rather than from HLA restricted CTL immune pressure. In Chapter 4, we report a novel method to sequence the entire locus of KIR3DL1/S1. Two specific pairs of primers have been successfully designed and tested to amplify KIR3DL1 and KIR3DS1 exclusively. Using this novel sequencing method, we showed the polymorphism of this locus at a 6-digit level. 8 new KIR3DS1 alleles, 12 new KIR3DL1 alleles, 1 new KIR3DL1 gene and 1 new KIR3DS1 gene have been identified in this study. In Chapter 5, we used a valuable acute HIV-1 infection cohort to further study associations between KIRs and the clinical outcomes. It was interesting to find that the frequency of KIR3DS1 was significantly lower in the slow progressors group (31%) than in the acute group (40.7%), which implies that KIR3DS1 plays a role in HIV-1 disease progression. There are two other trends demonstrated in this study. One trend was that positive KIR2DL2 and/or KIR2DS2 (they are in strong linkage disequilibrium with each other) were associated with a higher set point viral load (at 3 month) (p=0.06). Another trend was that KIR3DS1 might have an association with disease progression (p=0.057). Overall, in this study, the role of KIRs and KIR/HLA interactions were evaluated in acute and chronic HIV-1 infection, which has provided important information for further study.