Estimated glomerular filtration rate slopes on tenofovir alafenamide.

OBJECTIVES: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. METHODS: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time-updated CD4 cell count and HIV RNA measurements. RESULTS: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was -2.08 [95% confidence interval (CI) -2.24, -1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). CONCLUSIONS: Significant improvement in eGFR slope was observed in patients who switched from TDF- to TAF-containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.

A case of Kaposi sarcoma in an immunocompetent, heterosexual Irish man: a discussion of etiology and viral transmission.

Four types of Kaposi sarcoma (KS) have been described, all of which are caused by human herpesvirus-8 (HHV-8).  The incidence of KS in the United States is highest among HIV-positive homosexual men and elderly men of Eastern European, Jewish, or Mediterranean descent. However, few reports describe KS in HIV-negative, immunocompetent heterosexual men in the United States. HHV-8 is transmitted largely via saliva and close sexual contact, whereas there are only a handful of reports of transmission via blood and blood products. We report a case of an HIV-negative, immunocompetent heterosexual man who acquired KS via blood transfusion. A 77-year-old immunocompetent, monogamously heterosexual, HIV-negative Irish man presented with a biopsy-proven KS lesion on the right thigh. Past surgical history included a coronary artery bypass graft, during which he received a blood transfusion from an unknown donor source.  His ecchymotic KS lesions progressed while on doxycycline, intralesional vinblastine, and topical anti-angiogenic medications.  The patient eventually achieved stabilization of KS lesions with acitretin. Our case report emphasizes the need to characterize the phenotype and transmission route of HHV-8 in heterosexual, immunocompetent patients in geographic regions with low HHV-8 seroprevalence.

Breast cancer screening uptake among women from different ethnic groups in London: a population-based cohort study.

OBJECTIVE: To use newly available self-assigned ethnicity information to investigate variation in breast cancer screening uptake for women from the 16 specific ethnic groups within the broad Asian, Black and White groups that previous studies report. SETTING: National cancer screening programme services within London. PARTICIPANTS: 655,516 female residents aged 50-69, invited for screening between March 2006 and December 2009. Ethnicity information was available for 475,478 (72.5%). White British women were the largest group (306,689, 46.8%), followed by Indian (34,687, 5.3%), White Other (30,053, 4.6%), Black Caribbean (25,607, 3.9%), White Irish (17,271, 2.6%), Black African (17,071, 2.6%) and Asian Other (10,579, 1.6%). OUTCOME MEASURES: Uptake for women in different ethnic groups aged 50-52 for a first call invitation to the programme, and for women aged 50-69 for a routine recall invitation after a previous mammography. Uptake is reported (1) for London overall, adjusted using logistic regression, for age at invitation, socioeconomic deprivation and geographical screening area, and (2) for individual areas, adjusted for age and deprivation. RESULTS: White British women attended their first call (67%) and routine recall (78%) invitations most often. Indian women were more likely to attend their first (61%) or routine recall (74%) than Bangladeshi women (43% and 61%, respectively), and Black Caribbean women were more likely than Black African women to attend first call (63% vs 49%, respectively) and routine recall (74% vs 64%, respectively). There was less variation between ethnic groups in some screening areas. CONCLUSIONS: Breast cancer screening uptake in London varies by specific ethnic group for first and subsequent invitations, with White British women being more likely to attend. The variation in the uptake for women from the same ethnic groups in different geographical areas suggests that collaboration about the successful engagement of services with different communities could improve uptake for all women.

Ethnic variations in five lower gastrointestinal diseases: Scottish health and ethnicity linkage study.

OBJECTIVES: Our objective was to augment the limited evidence mainly from local, clinical studies of ethnic differences in gastrointestinal disorders. Our question was: are there ethnic variations in hospitalisation/death for lower gastrointestinal disorders in Scotland? SETTING: Scotland. POPULATION: This retrospective-cohort linked 4.65 (of 4.9) million people in the 2001 census of Scotland (providing data on ethnicity, country of birth and indicators of socioeconomic deprivation) to 9 years of National Health Service hospitalisation and death records. PRIMARY AND SECONDARY OUTCOME MEASURES AND ANALYSIS: For appendicitis, we studied all ages; for irritable bowel syndrome, ulcerative colitis, Crohn's disease and diverticular disease, we included those ≥20 years. Using Poisson regression (robust variance) we calculated, by ethnic group and sex, first-hospitalisation/death age-adjusted rates per 100,000 person-years, and relative risks (RRs) with 95% CIs multiplied by 100, so the White Scottish reference population had an RR=100. RESULTS: There were ethnic variations; for example, for irritable bowel syndrome, RRs (95% CIs) were comparatively high in Other White British women (128.4 (111.0 to 148.6)), and low in Pakistani women (75.1 (60.6 to 93.1)). For appendicitis, RRs were high in men in Other White British (145.2 (127.8 to 164.9)), and low in most non-White groups, for example, Pakistanis (73.8 (56.9 to 95.6)). For ulcerative colitis, RRs were high in Indian (169.8 (109.7 to 262.7)) and Pakistani (160.8 (104.2 to 248.2)) men. For Crohn's disease, the RR was high in Pakistani men (209.2 (149.6 to 292.6)). For diverticular disease, RRs were high in Irish men (176.0 (156.9 to 197.5)), and any Mixed background women (144.6 (107.4 to 194.8)), and low in most non-White groups, for example, Chinese men (47.1 (31.0 to 71.6) and women (46.0 (30.4 to 69.8)). CONCLUSIONS: Appendicitis and diverticular disease were comparatively low in most non-White groups, while ulcerative colitis and Crohn's disease were mostly higher in South Asians. Describing and understanding such patterns may help clinical practice and research internationally.

Does social disadvantage over the life-course account for alcohol and tobacco use in Irish people? Birth cohort study.

AIMS: Few studies have examined how the settlement experiences of migrant parents might impact on the downstream adult health of second-generation minority ethnic children. We used prospective data to establish if childhood adversity relating to the settlement experiences of Irish-born parents might account for downstream adverse health-related behaviours in second-generation Irish respondents in adulthood. DESIGN, SETTING AND PARTICIPANTS: Cohort data from the National Child Development Study, comprising 17 000 births from a single week in 1958, from Britain, were analysed. Respondents were followed to mid-life. Dependent variables were alcohol and tobacco use. The contribution of life-course experiences in accounting for health-related behaviours was examined. FINDINGS: Relative to the rest of the cohort, the prevalence of harmful/hazardous alcohol use was elevated in early adulthood for second-generation men and women, although it reduced by age 42. Second-generation Irish men were more likely to report binge alcohol use (odds ratio 1.45; 95% confidence interval 0.99, 2.11; P = 0.05), and second-generation Irish women were more likely to smoke (odds ratio 1.67; 95% confidence interval 1.23, 2.23; P = 0.001), at mid-life. Childhood disadvantage partially mediated associations between second-generation Irish status and mid-life alcohol and tobacco use, although these were modest for associations with smoking in Irish women. CONCLUSIONS: The findings suggest mechanisms for the intergenerational 'transmission' of health disadvantage in migrant groups, across generations. More attention needs to focus on the public health legacy of inequalities transferring from one migrant generation to the next.

Are Australian immigrants at a risk of being physically inactive?

BACKGROUND: We examined whether physical activity risk differed between migrant sub-groups and the Australian-born population. METHODS: Data were drawn from the Australian National Health Survey (2001) and each resident's country of birth was classified into one of 13 regions. Data were gathered on each resident's physical activity level in the fortnight preceding the survey. Multivariable logistic regression, adjusted for potential confounders examined the risk of physical inactivity of participants from each of the 13 regions compared to the Australian-born population. RESULTS: There was a greater prevalence of physical inactivity for female immigrants from most regions compared to male immigrants from a like region. Immigrants from South East Asia (OR 2.04% 95% CI 1.63, 2.56), Other Asia (OR 1.53 95% CI 1.10, 2.13), Other Oceania (1.81 95% CI 1.11, 2.95), the Middle East (OR 1.42 95% CI 0.97, 2.06 [note: border line significance]) and Southern & Eastern Europe are at a significantly higher risk of being physically inactive compared to those born in Australian. In contrast, immigrants from New Zealand (OR 0.77 95% CI 0.62, 0.94), the UK & Ireland (OR 0.82 95% CI 0.73, 0.92), and other Africa (OR 0.69 95% CI 0.51, 0.94) are at a significantly lower risk of being physically inactive compared to the Australian born population. CONCLUSION: Future research identifying potential barriers and facilitators to participation in physical activity will inform culturally sensitive physical activity programs that aim to encourage members of specific regional ethnic sub-groups to undertake physical activity.

Mitochondrial translation initiation factor 3 polymorphism and Parkinson's disease.

Mitochondrial dysfunction has been proposed to play a role in the pathogenesis of Parkinson's disease (PD). Supportive of this hypothesis, several genetic variants that regulate mitochondrial function and homeostasis have been described to alter PD susceptibility. A recent report demonstrated association of a single nucleotide polymorphism in the mitochondrial translation initiation factor 3 (MTIF3) gene with PD risk. The protein encoded by this nuclear gene is essential for initiation complex formation on the mitochondrial 55S ribosome and regulates translation of proteins within the mitochondria. Changes in the function or expression of the MTIF3 protein may result in altered mitochondrial function, ATP production or formation of reactive oxygen species thereby affecting susceptibility to PD. We examined the association of rs7669 with sporadic PD in three Caucasian case control series (n=2434). A significant association was observed in the largest series (Norwegian; n=1650) when comparing CC vs. CT/TT genotypes, with the Irish and US series having a similar but non-significant trend. The combined series also revealed an association with risk of PD (P=0.01), supporting the possible involvement of this gene in PD etiology.

Cultural factors related to smoking in San Francisco's Irish bars.

California's Smoke-Free Workplace Act was extended to include bars in 1998. While the majority of bars in the state have become smoke free, in many bars patrons and staff continue to smoke despite the law. The authors present findings from a study which assessed cultural factors related to continued smoking in bars in the city of San Francisco. In bars serving primarily Irish migrants, tight-knit relations within the local Irish bar community together with a reluctance to be the first Irish bar to ban smoking were found to contribute to continued indoor smoking. The findings illustrate challenges to implementing tobacco control policies within ethnic subpopulations and particularly highlight the importance of considering how cultural dynamics within subpopulations may help or hinder such policies.

HLA-A, B, Cw, DRB1, DQB1 and DPB1 alleles and haplotypes in the genetically homogenous Irish population.

The frequencies of human leucocyte antigen (HLA) class I and II alleles and haplotypes of 250 Irish unrelated bone marrow donors were determined by high resolution polymerase chain reaction (PCR), using a combination of reverse line blot hybridization and PCR with sequence-specific primers. Phylogenetic analyses indicate that this Irish population is closely related to British, North-western European, American and Australian Caucasian populations. These observations are consistent with recognized historical, geographical, cultural, ethnic and linguistic relationships between these populations and suggest that Irish haematopoietic stem cell transplant recipients have a greater likelihood of finding a phenotypically matched donor within registries based on these populations. HLA-A, B, Cw, DRB1, DQB1 and DPB1 analysis confirms that this young homogenous population is characterized by features of a North-western European anthropological type with limited influence of additional ethnic haplotypes.

Is the histidine triad nucleotide-binding protein 1 (HINT1) gene a candidate for schizophrenia?

BACKGROUND: : The histidine triad nucleotide-binding protein 1, HINT1, hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate. The human HINT1 gene is located on chromosome 5q31.2, a region implicated in linkage studies of schizophrenia. HINT1 had been shown to have different expression in postmortem brains between schizophrenia patients and unaffected controls. It was also found to be associated with the dysregulation of postsynaptic dopamine transmission, thus suggesting a potential role in several neuropsychiatric diseases. METHODS: : In this work, we studied 8 SNPs around the HINT1 gene region using the Irish study of high density schizophrenia families (ISHDSF, 1350 subjects and 273 pedigrees) and the Irish case control study of schizophrenia (ICCSS, 655 affected subjects and 626 controls). The expression level of HINT1 was compared between the postmortem brain cDNAs from schizophrenic patients and unaffected controls provided by the Stanley Medical Research Institute. RESULTS: : We found nominally significant differences in allele frequencies in several SNPs for both ISHDSF and ICCSS samples in sex-stratified analyses. However, the sex effect differed between the two samples. In expression studies, no significant difference in expression was observed between patients and controls. However, significant interactions amongst sex, diagnosis and rs3864283 genotypes were observed. CONCLUSION: : Data from both association and expression studies suggested that variants at HINT1 may be associated with schizophrenia and the associations may be sex-specific. However, the markers showing associations were in high LD to the SPEC2/PDZ-GEF2/ACSL6 locus reported previously in the same samples. This made it difficult to separate the association signals amongst these genes. Other independent studies may be necessary to distinguish these candidate genes.

Analysis and application of European genetic substructure using 300 K SNP information.

European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA) showed the largest division/principal component (PC) differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA) analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.

Indigenous ethnic minorities and palliative care: exploring the views of Irish Travellers and palliative care staff.

Indigenous people are among the ethnic minorities who encounter palliative care services. This research shows that Irish Travellers have little experience of specialist palliative care and that specialist palliative care providers have little knowledge or experience of Irish Travellers. Characteristics of Irish Travellers culture including the importance of hope, avoidance of open acknowledgment of death, the importance of family and the avoidance of the place of death (including moving away or burning caravans where death has occurred) challenge the provision of specialist palliative care. Individualisation of patient care, a feature of specialist palliative care can help staff provide appropriate care.

Potential barriers to prevention of cancers and to early cancer detection among Irish people living in Britain: a qualitative study.

OBJECTIVES: To identify and explore explanatory models of cancer among Irish and white British people living in Britain. METHODS: Ethnographic in-depth interviews and focus groups were conducted in London, Manchester and Glasgow, with a total of 58 (n = 58) Irish and 57 (n = 57) white British participants. The study samples were broadly similar in socio-demographic characteristics. RESULTS: We explored explanatory models (lay beliefs) used by the Irish and white British to understand their cancer-related beliefs and behaviours. Among both groups there was confusion about causation, poor knowledge of signs and symptoms, and a general pessimism about cancer prevention and treatments. The narratives of the Irish were, however, qualitatively different from those of the white British. Historical, cultural, social and economic circumstances, both in the UK and in the past in Ireland, appeared to influence views of cancer and health-seeking behaviours. Recollections of negative family experiences of cancers linked to 'stigma' and 'secrecy', poor outcomes and medical practices in rural Ireland, particularly among the older Irish, influenced Irish understanding of cancers and help-seeking behaviours. The second generation also appeared to retain some beliefs that were common amongst the first generation migrants. The context of migration was also felt by the Irish group to have exposed them to living and working environments that made them susceptible to cancers. CONCLUSION: The Irish frame of reference was firmly embedded in a specific historical, social and economic context which may contribute to cultural constraints on discussions about cancers and to the lack of engagement with preventative behaviours and health care services.

Ancestry reported by white adults with cutaneous melanoma and control subjects in central Alabama.

BACKGROUND: We sought to evaluate the hypothesis that the high incidence of cutaneous melanoma in white persons in central Alabama is associated with a predominance of Irish and Scots descent. METHODS: Frequencies of country of ancestry reports were tabulated. The reports were also converted to scores that reflect proportional countries of ancestry in individuals. Using the scores, we computed aggregate country of ancestry indices as estimates of group ancestry composition. HLA-DRB1*04 allele frequencies and relationships to countries of ancestry were compared in probands and controls. Results were compared to those of European populations with HLA-DRB1*04 frequencies. RESULTS: Ninety evaluable adult white cutaneous melanoma probands and 324 adult white controls reported countries of ancestry of their grandparents. The respective frequencies of Ireland, and Scotland and "British Isles" reported countries of ancestry were significantly greater in probands than in controls. The respective frequencies of Wales, France, Italy and Poland were significantly greater in controls. 16.7% of melanoma probands and 23.8% of controls reported "Native American" ancestry; the corresponding "Native American" country of ancestry index was not significantly different in probands and controls. The frequency of HLA-DRB1*04 was significantly greater in probands, but was not significantly associated with individual or aggregate countries of ancestry. The frequency of DRB1*04 observed in Alabama was compared to DRB1*04 frequencies reported from England, Wales, Ireland, Orkney Island, France, Germany, and Australia. CONCLUSION: White adults with cutaneous melanoma in central Alabama have a predominance of Irish, Scots, and "British Isles" ancestry and HLA-DRB1*04 that likely contributes to their high incidence of cutaneous melanoma.

Cardiovascular risk profiles in UK-born Caribbeans and Irish living in England and Wales.

Cardiovascular disease is the leading cause of morbidity and mortality among Caribbean and Irish origin people living in England and Wales. Yet mortality from coronary heart disease (CHD) of migrant Caribbeans is lower than the national average, while stroke mortality is higher. The Irish experience higher than average mortality from both diseases. Little is known about the health of the children of these migrants. The Health Survey for England (HSE) 1999 was used to investigate for the first time cardiovascular risk factors in UK-born Caribbeans aged 35-44 and Irish aged 35-44 and 45-54 years. Caribbean men were more likely to smoke but had higher mean HDL-cholesterol than men in the general population. Caribbean women had greater body mass indices and lower mean triglyceride levels. Irish men in both age groups smoked more than men in the general population, but in the younger group had lower diastolic blood pressure (BP). At age 35-44 only, Irish women were shorter than women in the general population. These findings were independent of differences in socio-economic position. Previously, Caribbean-born migrants to Britain had generally favourable lipid profiles in line with lower CHD rates, despite obesity and diabetes. The nationally representative but small-scale data presented here suggest that UK-born Caribbeans appear to be losing this more favourable lipid pattern and among men smoking rates are now higher compared with general population men, suggesting that an increase in CHD rates can be expected. Further research should examine how improved education and specific intervention programs could be used to reduce smoking among UK-born Irish and Caribbean men, and obesity among UK-born Caribbean women. The next HSE also needs to include adequate numbers of younger people of different ethnic origins to allow time trends in these anthropometric, behavioural and metabolic risk factors to be examined reliably and fully.

Comparison of the CFTR mutation spectrum in three cohorts of patients of Celtic origin from Brittany (France) and Ireland.

This study aims to compare the spectrum of the mutations identified in the gene responsible for cystic fibrosis in three cohorts of patients of Celtic origin from Brittany and Ireland. It included 389 patients from Brittany, 631 from Dublin and 139 from Cork. The CFTR gene analysis relied on the detection of the most common mutations, followed by a complete gene scanning using DGGE or D-HPLC. High mutation detection rates were obtained in each cohort: 99.6%, 96.8%, and 96.0% respectively. A high frequency of the c.1652_1655 del3 mutation (F508del: 74.8% to 81.3%) and of the "Celtic" mutation (c.1784G>A (G551D): 3.7% to 9.7%) was observed in each population. Apart from this, the mutation spectrums differed. In Brittany, the most common abnormalities were: c.1078delT (3.6%), c.4041C>G (N1303K: 1.4%), c.2670G>A (W846X(2): 1.0%) and c.1717-1G>A (1.0%), whereas in the cohort of Dublin, the main mutations were: c.482G>A (R117H: 3.0%), c.1811G>C (R560T: 2.4%) and c.621+1G>T (1.7%). Finally, in the Cork area, only the c.482G>A mutation (R117H) reached a frequency of 1%. Two previously-unreported mutations were identified in the Dublin cohort: c.2623-2A>G and c.3446T>G (M1105R). This collaborative study highlights the similarities of the CFTR alleles in the Breton and Irish populations, but also the disparities that exist between these populations, despite their common origin. Each population has its own history, with its mixture of founder effects and genetic drifts, which are at the origin of the current mutation distribution. The molecular study of the CFTR gene provides new tools for retracing European populations' histories.

Sunbathing intentions in Irish people travelling to Mediterranean summer holiday destinations.

As exposure to UV light is thought to be the most significant environmental and behavioural risk factor for avoiding skin cancer, we have analysed the sunbathing intentions and attitudes of Irish people travelling to Mediterranean and Iberian holiday destinations. Ninety per cent of respondents planned to get a suntan on their vacation with 44% likely to burn their skin in the process. Although all intended to apply sun cream on holiday only 40% would apply >SPF 15. Sixty-four per cent planned to sunbathe between 11.00 am and 3.00 pm, with 25% intending to spend <5 hours in the sun. One-third of those intending to sunbathe for >6 hours per day were aged between 16 and 24 years. Approximately eight out of 10 people thought suntans made them feel healthier or attractive. Fifty-six per cent regularly checked their moles but men were less likely to check their skin for pigment changes. The results provide baseline information on sunbathing attitudes of Irish people. They show that while most people feel they adopt a careful approach to sunbathing, the experiences and intentions, especially in younger people, are influenced by the desirability of a suntan, and reflect a behaviour that increases their risk of skin cancer.

A review of ethnicity, health and nutrition-related diseases in relation to migration in the United Kingdom.

OBJECTIVES: To identify lessons from and gaps in research on diet-disease links among former migrants in the United Kingdom (UK). RESULTS: Migrant status and self-identified ethnicity do not match so these terms mask differences in social, nutritional and health status within and between population groups. Some former migrants differ in causes of death from the general population, e.g.: fewer coronary heart disease deaths among Caribbean-born; fewer cancer deaths among Caribbean, South Asian- and East African-born adults. Irish- and Scottish-born have higher mortality from all causes. Experience of risk factors differ also, e.g.: higher prevalences of hypertension and diabetes in Caribbean- and South Asian-born adults than representative samples of the general population; obesity and raised waist-hip circumference ratios in South Asian, African-Caribbean and some Irish-born adults. Former migrants experience long-term disadvantage, associated with more self-defined illness and lower reported physical activity. Nutrient intake data from the few, recent, small-scale studies must be interpreted with caution due to methodological diversity. However, second generation offspring of former migrants appear to adopt British dietary patterns, increasing fat and reducing vegetable, fruit and pulse consumption compared with first generation migrants. CONCLUSIONS: There is insufficient evidence on why some former migrants but not others experience lower specific mortality than the general population. Dietary intake variations provide important clues particularly when examined by age and migration status. Majority ethnic and younger migrant groups could raise and sustain high fruit and vegetable intakes but lower proportions of fat, by adopting many dietary practices from older migrants. Objective measures of physical activity and longitudinal studies of diets among different ethnic groups are needed to explain diversity in health outcomes and provide for evidence-based action.

Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation.

Infantile nephropathic cystinosis, an autosomal recessive disease characterized by a lysosomal accumulation of cystine, presents as failure to thrive, rickets and proximal renal tubular acidosis. The cystinosis gene, CTNS, which maps to chromosome 17p13, encodes a predicted 55 kDa protein with characteristics of a lysosomal membrane protein. We have conducted extensive linkage analysis in a French Canadian cystinosis cohort identifying a founding haplotype present in approximately half (21/40) of the chromosomes studied. Subsequent mutational analysis, in addition to identifying two novel mutations, has unexpectedly revealed a mutation which has been previously found in Irish (but not French) cystinotic families on these 21 French Canadian chromosomes. Haplotype analysis of two Irish families with this mutation supports the hypothesis that Celtic chromosomes represent an extensive portion of cystinosis chromosomes in French Canada. Our analysis underlines the genetic heterogeneity of the French Canadian population, reflecting a frequently unrecognized contribution from non-Gallic sources including the Irish.