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Copy number variations can be identified using newer genotyping arrays with higher single nucleotide polymorphisms (SNPs) density and copy number probes accompanied by newer algorithms. McCarroll et al. (2008) applied these to the HapMap II samples and identified 1316 copy number polymorphisms (CNPs). In our study, we applied the same approach to 859 samples from three Singapore populations and seven HapMap III populations. Approximately 50% of the 1291 autosomal CNPs were found to be polymorphic only in populations of non-African ancestry. Pairwise comparisons among the 10 populations showed substantial differences in the CNPs frequencies. Additionally, 698 CNPs showed significant differences with false discovery rate (FDR)<0.01 among the 10 populations and these loci overlap with known disease-associated or pharmacogenetic-related genes such as CFHR3 and CFHR1 (age related macular degeneration), GSTTI (metabolism of various carcinogenic compounds and cancers) and UGT2B17 (prostate cancer and graft-versus-host disease). The correlations between CNPs and genome-wide association studies-SNPs were investigated and several loci, which were previously unreported, that may potentially be implicated in complex diseases and traits were found; for example, childhood acute lymphoblastic leukaemia, age-related macular degeneration, breast cancer, response to antipsychotic treatment, rheumatoid arthritis and type-1 diabetes. Additionally, we also found 5014 novel copy number loci that have not been reported previously by McCarroll et al. (2008) in the 10 populations.

The abundance of copy number variants (CNVs) and regions of homozygosity (ROHs) have been well documented in previous studies. In addition, their roles in complex diseases and traits have since been increasingly appreciated. However, only a limited amount of CNV and ROH data is currently available for the Swedish population. We conducted a population-based study to detect and characterize CNVs and ROHs in 87 randomly selected healthy Swedish individuals using the Affymetrix SNP Array 6.0. More than 600 CNV loci were detected in the population using two different CNV-detection algorithms (PennCNV and Birdsuite). A total of 196 loci were consistently identified by both algorithms, suggesting their reliability. Numerous disease-associated and pharmacogenetics-related genes were found to be overlapping with common CNV loci such as CFHR1/R3, LCE3B/3C, UGT2B17 and GSTT1. Correlation analysis between copy number polymorphisms (CNPs) and genome-wide association studies-identified single-nucleotide polymorphisms also indicates the potential roles of several CNPs as causal variants for diseases and traits such as body mass index, Crohn's disease and multiple sclerosis. In addition, we also identified a total of 14 815 ROHs 500 kb or 2814 ROHs 1M in the Swedish individuals with an average of 170 and 32 regions detected per individual respectively. Approximately 141 Mb or 4.92% of the genome is homozygous in each individual of the Swedish population. This is the first population-based study to investigate the population characteristics of CNVs and ROHs in the Swedish population. This study found many CNV loci that warrant further investigation, and also highlighted the abundance and importance of investigating ROHs for their associations with complex diseases and traits.

Motivation: With the expansion of whole-genome studies, there is rapid evolution of genotyping platforms. This leads to practical issues such as upgrading of genotyping equipment which often results in research groups having data from different platforms for the same samples. While having more data can potentially yield more accurate copy-number estimates, combining such data is not straightforward as different platforms show different degrees of attenuation of the true copy-number or different noise characteristics and marker panels. Currently, there is still a relative lack of procedures for combining information from different platforms., Results: We develop a method, called MPSS, based on a correlated random-effect model for the unobserved patterns and extend the robust smooth segmentation approach to the multiple-platform scenario. We also propose an objective criterion for discrete segmentation required for downstream analyses. For each identified segment, the software reports a P-value to indicate the likelihood of the segment being a true CNV. From the analyses of real and simulated data, we show that MPSS has better operating characteristics when compared to single-platform methods, and have substantially higher sensitivity compared to an existing multiplatform method., Availability: The methods are implemented in an R package MPSS, and the source is available from http://www.meb.ki.se/~yudpaw.

Regions of homozygosity (ROHs) are more abundant in the human genome than previously thought. These regions are without heterozygosity, i.e. all the genetic variations within the regions have two identical alleles. At present there are no standardized criteria for defining the ROHs resulting in the different studies using their own criteria in the analysis of homozygosity. Compared to the era of genotyping microsatellite markers, the advent of high-density single nucleotide polymorphism genotyping arrays has provided an unparalleled opportunity to comprehensively detect these regions in the whole genome in different populations. Several studies have identified ROHs which were associated with complex phenotypes such as schizophrenia, late-onset of Alzheimer's disease and height. Collectively, these studies have conclusively shown the abundance of ROHs larger than 1 Mb in outbred populations. The homozygosity association approach holds great promise in identifying genetic susceptibility loci harboring recessive variants for complex diseases and traits.

Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease with renal involvement being one of the most frequent and serious manifestations of the disease. The aim of the study is to analyze the treatment and renal outcome of patients with lupus nephritis (LN) WHO class III and IV on cyclophosphamide (CYC). We retrospectively identified 41 patients with biopsy proven LN who was given either oral or intravenous CYC. The male: female ratio was 4:37; with a mean age of 31.7 +/- 9.8 years at presentation. 36 patients (87.8%) had LN class IV and only five patients (12.2%) with LN class III. The mean serum creatinine at presentation was 87.4 +/- 37.2 micromol/L with mean follow-up of 84 +/- 78 months. A total of 30 patients (73.2%) completed 12 courses of IV CYC and one patient (2.4%) completed three months of oral CYC. 71.0% (n = 22) had complete response (CR), 25.8% (n = 8) had partial response and 3.2% (n = 1) had no response (NR). Of the remaining 11 patients, two patients (4.9%) died during the treatment, three patients (7.3%) defaulted treatment and five patients (12.2%) are still receiving ongoing treatment. Presence of hypertension (p < 0.003) and evidence of chronicity on renal biopsy (p < 0.016) were significantly correlated with the progressive deterioration of renal function in our population. In conclusion, hypertension and evidence of chronicity on renal biopsy, proved to be risk factors for progressive renal impairment in our study population. The achieved global outcome can be considered good.

Background: The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis., Methods: Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were randomly assigned to either mycophenolate mofetil (MMF) 2 g/day for 6 months or intravenous cyclophosphamide (IVC) 0.75-1 g/m(2) monthly for 6 months in addition to corticosteroids., Results: Remission occurred in 13 out of 25 patients (52%) in the IVC group and 11 out of 19 patients (58%) in the MMF group (P = 0.70). There were 12% in the IVC group and 26% in the MMF group that achieved complete remission (P = 0.22). Improvements in haemoglobin, the erythrocyte sedimentation rate, serum albumin, serum complement, proteinuria, urinary activity, renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups. Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups. The chronicity index increased in both groups but was only significant in the IVC group. Adverse events were similar. Major infections occurred in three patients in each group. There was no difference in gastrointestinal side-effects., Conclusions: MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis.

Objectives: To compare patient graft survival between various subgroups among renal transplant patients., Patients and Methods: A retrospective analysis of all renal transplant patients from January 1, 1993, to June 1, 2003, was performed using follow-up records and data submitted to the National Renal Registry., Results: A total of 91 renal transplant patients were followed, with a male-to-female ratio of 57:34 (62.6%:37.4%) and mean age at transplant 35.6 +/- 12.1 years (range 10.1-64.4 years) with 38 (41.8%) cases transplanted locally and 53 (58.2%) cases transplanted overseas, of which 36 (39.6%) were from live donors and the remaining 55 (60.4%) from cadavers. As of June 1, 2003, 50 transplant patients are on regular follow-up, with 41 patients lost due to 12 (29.3%) deaths, 16 (39.0%) graft failures, 11 (26.8%) transfers, and 2 (4.9%) lost to follow-up. Overall patient and graft survival rates at 2, 5, and 10 years were 93.1%, 77.4%, and 49.2%, respectively. Survival rates for male transplant patients were 91.4%, 71.9%, and 46.7% compared to 96.1%, 86.9%, and 53.6% for females. Survival rates for Malay race patients were 92.0%, 59.5%, and 28.6%; Chinese rates were 96.0%, 81.6%, and 54.8%, and Indian rates were 81.0%, 81.0%, and 46.3%, respectively. The survivals for transplants from living donors were 96.9%, 85.6%, and 62.3% compared to cadaveric kidney transplants namely 89.9%, 71.3%, and 35.0%. The local transplant survival rates were 96.9%, 82.3%, and 60.8% compared to overseas transplants, with survival rates of 89.9%, 73.5%, and 35.7%. Finally, living-related donor transplantation survival rates were 96.8%, 84.9%, and 62.2% compared to nonrelated donors-90.1%, 71.3%, and 35.0%-at 2 years, 5 years, and 10 years, respectively., Conclusion: Overall survival has been good. The survival rates were better among female gender, Chinese race, local transplantation, and kidneys from living-related donors.

We report here a case of a kidney transplant recipient in whom the ureter was initially implanted into the peritoneum. Excessive ultrafiltration volume and reversal of serum vs dialysate creatinine ratio when the patient was recommenced on continuous ambulatory peritoneal dialysis first suggested the diagnosis which was subsequently confirmed by a plain abdominal x-ray demonstrating placement of ureteric stent in the peritoneum. This rare complication was successfully corrected with surgical re-implantation of ureter into the bladder and 5 years later, the patient remains well with good graft function.

There were 72 pregnancies in 46 renal transplants (RTs) between 1984 and 2001, 89% from living donors, 11% cadaveric. Mean age at RT was 26.9 +/- 4.3 years and at pregnancy 30.7 +/- 4.7 years. Mean time to pregnancy after RT was 4.5 +/- 3.1 years. 54% were unplanned. 45 (63%) resulted in surviving infants, 37% delivered by Caesarean section. 35% were premature. Mean birth weight was 2.38 +/- 0.57 kg. 64% were on cyclosporine. No patient had an acute rejection during pregnancy; 38% had pre-existing hypertension. Complications include urinary infection (13%), proteinuria (15%) and preeclampsia (15%). Mean serum creatinine before pregnancy was 112.7 +/- 32.6 umol/l, 1 year post-pregnancy it was 119.4 +/- 38.7. The mean time of follow up of mothers is 4.9 +/- 3.5 years. 10 year graft survival was 83% and patient survival 94%.