Knowledge and attitudes regarding genetic testing among Jordanians: An approach towards genomic medicine

BackgroundThe twenty first century can be called the genomic era referring to the rapid development of genetics, and the beginning of genomic medicine. An initial step towards genomic medicine is to evaluate the knowledge and attitude towards genetic testing among different populations. The aims of this study were to assess the genetic knowledge and attitude towards genetic testing among the Jordanian population and patients with immune diseases. In addition, we evaluated the association between knowledge, attitude and several demographic factors of the population.MethodsThis study was performed using an online questionnaire that was distributed to respondents from different regions of Jordan.ResultsA total of 1149 participants were recruited from the Jordanian population. Overall factual genetic knowledge of the participants was good (65.4%), with education level, working or studying in a health-related field and household average monthly income being significant predictors of factual knowledge scores (P = 0.03, P < 0.001 and P < 0.001, respectively). However, factual knowledge results revealed that scores of questions related to diseases were significantly higher than scores of gene-related scientific facts (P < 0.01). Participants of our study reported to have low perceived knowledge on medical uses (39.5%) and social consequences (23.9%) of genetic testing. Regarding the participants’ attitudes, favorable attitudes towards genetic testing were prevailing (91.5%). Favorable attitudes were more prominent among higher educated participants, and participants with higher scores of factual knowledge.ConclusionDespite the fact that our Jordanian-based study revealed a good level of genetic knowledge as well as a favorable attitude towards genetic testing, we realized an imbalance of knowledge between gene-related scientific facts and disease-related concepts as well as between factual and perceived genetic knowledge, which indicates the necessity of increasing the awareness about genetic testing in order to ensure that individuals can take informed decisions that help in the employment of personalized medicine.     

Impact of polycystic ovary syndrome on eating behavior,depression and health related quality of life: A cross-sectional study in Riyadh

Background & objectivesPolycystic ovary syndrome (PCOS) is the most common endocrinal disorder, and the greatest cause of infertility in women. Despite availability of individual data on impact of multiple endocrinal, reproductive and even metabolic factors in PCOS individuals, the data on the co-existence of BED and depression in PCOS patients with its relationship on the quality of life in Saudi Arabian females is not found. Hence this study is aimed to elucidate the implication of PCOS on eating behaviour, induction of depression and general health quality in Saudi Arabian population of Riyadh.Materials and methodsThis is a cross-sectional study carried out in multiple health facilities of Riyadh from January to March 2019. The study samples (494) were recruited by convenience sampling and administered validated questionnaire by trained research participants. The data obtained was analysed by binary logistic regression using SPSS-IBM 25.ResultsOf the total 494 women participated in the study, 23.48% (116) were PCOS individuals. The odds of developing abnormal health related quality of (HRQ) in patients with PCOS was significantly (P = 0.000, OR = 3.472) high when compared to non-PCOS participants. The odds of showing high binge eating disorder (BED, P = 0.007, OR = 2.856) and depression (P = 0.000, OR = 2.497) scores in PCOS participants were significantly more than patients who were not having PCOS. Out of the three parameters studied, abnormal health related quality of life possessed a higher influence of PCOS compared to depression and abnormal eating behavior.Interpretation & conclusionIn conclusion, the present study shows that women with PCOS are at a significant risk for depressive disorders, disorganized eating behavior and impaired quality of life. Therefore, necessary care and screening is required to minimize the impact of PCOS on already burdened individuals.     

Prevalence and predictors of non-alcoholic fatty liver disease in tertiary care hospital of Taif,Saudi Arabia: A retrospective study

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) in Saudi Arabia is predicted to exceed 30% by 2030. NAFLD leads to liver fibrosis, thus increasing morbidity and health care burden. Obesity and diabetes have been strongly associated with NAFLD in different cities in Saudi Arabia.ObjectivesTherefore, we aim to determine the prevalence rate of NAFLD and specific risk factors for NAFLD among patients of tertiary care hospital of Taif city.Material and methodsWe retrospectively analyzed the medical records of patients for two years, between Feb 2017 and Feb 2019, (n = 100) referred to the hepatology clinic at King Abdulaziz Specialist Hospital in Taif. The diagnosis of NAFLD was based on the radiology report for patients who were aged >20 years old. Other parameters including fasting blood glucose (FBG), platelets count, alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin were statistically analyzed.ResultsWe found that 40% (P < 0.05) of all patients had NAFLD. The results revealed that a significantly high number of patients with NAFLD have high FBG levels (75%, P < 0.0001) and total bilirubin (P < 0.05). Meanwhile, platelet count was significantly reduced in patients with NAFLD (P < 0.05).ConclusionNAFLD can be a serious health problem in the Taif region. In addition, high FBG is a significant specific risk factor for NAFLD. Health care providers should pay more attention to limiting the prevalence of NAFLD and its risk factors.     

Genetic diversity and geographic differentiation of disjunct Atlantic and Amazonian populations of <Emphasis Type="Italic">Psychotria ipecacuanha</Emphasis> (Rubiaceae)

Ipecac (Psychotria ipecacuanha) is a perennial, medicinal herb that grows in the understory of semi-deciduous tropical forests in the Neotropics. Ipecacs present a widely disjunct distribution, with two of its three ranges occurring in Brazil. The Amazonian populations are at least 1600 km from the nearest Atlantic populations. This work used ISSR markers to compare the genetic diversity and structure of populations from the two Brazilian ranges. Lower genetic diversity in Amazon populations (P = 60.11%, Hs = 0.18) and higher genetic diversity in Atlantic populations (P = 73.94%, Hs = 0.20) were detected. Differentiation between ranges were high (θ ^B = 0.6838, G_ST-B = 0.6665). AMOVA revealed that 65.3% of the total molecular variance can be attributed to regional differences between the two ranges. Principal coordinate analyses and cluster analyses organized ipecacs at either individual or population level into two exclusive groups that correspond each to one of the two disjunct ranges, without exception. The results do not support a scenario that postulates human-mediated, long-distance dispersal events as a plausible origin for the distribution of the Brazilian ipecacs, but indicate geographic isolation as a long-standing barrier to genetic exchange and connectivity among populations from different ranges. Conservation implications are discussed.     

Populations genetic structure of the razor clam Sinonovacula constricta from China,Korea and Vietnam

The population genetic structure of the razor clam Sinonovacula constricta was investigated between populations collected from China, Korea and Vietnam using cytochrome oxidase subunit 1 (COI) mtDNA and internal transcribed spacer 2 (ITS2) rDNA markers. A total of 622 bp of COI and 495 bp of ITS2 were sequenced. Highly significant Fst values and low rates of migration were observed from populations between Vietnam and China, (Fst = 0.7578, P < 0.001, Nm = 0.05 for COI; Fst = 0.91389, P < 0.001, Nm = 0.07 for ITS2) and Korea (Fst = 0.79783, P < 0.001, Nm = 0.07 for COI; Fst = 0.74143, P < 0.001, Nm = 0.03 for ITS2). However, lower Fst values and higher gene flow were detected between populations from China and Korea (Fst = 0.25733, P < 0.001, Nm = 0.73) based on COI analysis. The similar pattern was also captured by ITS2 rDNA marker. In addition, Neighbor-joining phylogenetic tree analysis of the two markers resulted in one cluster consisting of haplotypes from Vietnam, and a second group comprising haplotypes from China and Korea. This research revealed a closer genetic relationship between clam population from China and Korea but less similarity to population from Vietnam.     

Deleterious effect of angiotensin-converting enzyme gene polymorphism in vitiligo patients

Vitiligo is a rare skin condition caused by an immune reaction. Vitiligo can occur anywhere on the body. This proposed explanation of vitiligo makes it clear that vitiligo is not linked to any other autoimmune diseases. The polymorphisms of some genes present in the immune system play a major function in susceptibility of vitiligo. Meta-analysis studies have shown that the Angiotensin converting enzyme (ACE) gene insertion and deletion polymorphism is closely associated with vitiligo in many ethnicities. The connection between ACE gene and vitiligo is connected through the auto immune diseases and there are no genetic polymorphism studies have been carried out with ACE gene with vitiligo in the Saudi population. Previous studies show that vitiligo patients are more likely to also have an autoimmune disorder. The current study aims to investigate the I/D polymorphism in the ACE gene with diagnosed patients with vitiligo subjects. This is a case-control study carried out in the Saudi population with 100 vitiligo cases and 100 healthy controls. Genotyping was performed through polymerase chain reaction followed by 3% agarose gel electrophoresis. Genotype and allele frequencies were carried out with genetic mode of inheritances. Statistical analysis was performed considering p < 0.05 as significant association. There was a substantial difference in allele frequency distribution between vitiligo patients and healthy controls (OR-1.70 (95%CI: 1.14–2.53); p = 0.008). Additionally, DD genotype (OR-4.71 (95%CI: 1.42–15.61); p = 0.008) and recessive model (OR-2.66 (95%CI: 1.41–5.02); p = 0.002) was strongly associated. Both dominant and co-dominant showed the negative association (p > 0.05) when compared between the vitiligo cases and controls. The correlation between age and genotyping was performed with Anova analysis and current study results confirmed the substantial link between 11 and 20 years (p = 0.01) and 31–40 years (p = 0.04) with the defined age groups. In conclusion, in Saudi populations, the ACE gene I/D polymorphism was identified as being correlated with vitiligo. This is the first study in Saudi Arabia to report the risk factors of vitiligo with the ACE gene polymorphism.     

Genetic diversity of North American captive‐born gorillas (Gorilla gorilla gorilla)

Western lowland gorillas (Gorilla gorilla gorilla) are designated as critically endangered and wild populations are dramatically declining as a result of habitat destruction, fragmentation, diseases (e.g., Ebola) and the illegal bushmeat trade. As wild populations continue to decline, the genetic management of the North American captive western lowland gorilla population will be an important component of the long‐term conservation of the species. We genotyped 26 individuals from the North American captive gorilla collection at 11 autosomal microsatellite loci in order to compare levels of genetic diversity to wild populations, investigate genetic signatures of a population bottleneck and identify the genetic structure of the captive‐born population. Captive gorillas had significantly higher levels of allelic diversity (t₇ = 4.49, P = 0.002) and heterozygosity (t₇ = 4.15, P = 0.004) than comparative wild populations, yet the population has lost significant allelic diversity while in captivity when compared to founders (t₇ = 2.44, P = 0.04). Analyses suggested no genetic evidence for a population bottleneck of the captive population. Genetic structure results supported the management of North American captive gorillas as a single population. Our results highlight the utility of genetic management approaches for endangered nonhuman primate species.     

Combined analyses of kinship and FST suggest potential drivers of chaotic genetic patchiness in high gene‐flow populations

We combine kinship estimates with traditional F‐statistics to explain contemporary drivers of population genetic differentiation despite high gene flow. We investigate range‐wide population genetic structure of the California spiny (or red rock) lobster (Panulirus interruptus) and find slight, but significant global population differentiation in mtDNA (Φ_ST = 0.006, P = 0.001; D_{est_Chao} = 0.025) and seven nuclear microsatellites (F_ST = 0.004, P < 0.001; D_{est_Chao} = 0.03), despite the species’ 240‐ to 330‐day pelagic larval duration. Significant population structure does not correlate with distance between sampling locations, and pairwise F_ST between adjacent sites often exceeds that among geographically distant locations. This result would typically be interpreted as unexplainable, chaotic genetic patchiness. However, kinship levels differ significantly among sites (pseudo‐F_16,988 = 1.39, P = 0.001), and ten of 17 sample sites have significantly greater numbers of kin than expected by chance (P < 0.05). Moreover, a higher proportion of kin within sites strongly correlates with greater genetic differentiation among sites (D_{est_Chao}, R² = 0.66, P < 0.005). Sites with elevated mean kinship were geographically proximate to regions of high upwelling intensity (R² = 0.41, P = 0.0009). These results indicate that P. interruptus does not maintain a single homogenous population, despite extreme dispersal potential. Instead, these lobsters appear to either have substantial localized recruitment or maintain planktonic larval cohesiveness whereby siblings more likely settle together than disperse across sites. More broadly, our results contribute to a growing number of studies showing that low F_ST and high family structure across populations can coexist, illuminating the foundations of cryptic genetic patterns and the nature of marine dispersal.     

Ultrasonographic fetal parameters and neonatal survival in somatic cell nuclear transfer–derived beef calves

The objectives of this study were to identify prognostic indicators of calf survival in SCNT-derived beef calves. Ultrasonographic parameters of fetal well-being and development, maternal clinical parameters, and neonatal parameters were evaluated as predictors of calf survival in cows carrying SCNT-derived beef fetuses (n = 38). Calf survival was 61.5% (88.2% female and 40.9% male calves; P = 0.0026). Cow respiratory rate and cow temperature were significantly greater in the nonsurviving (NS) group 1 week prepartum. In surviving (S) calves, fetal heart rate (FHR) decreased during the last 2 weeks of gestation (P < 0.01). However, this final deceleration was not observed in NS calves, resulting in higher FHRs in this group (P < 0.0001). Fetal movement and fluid scores did not differ with calf classification. Mean amniotic fluid depth was smaller in S (5.5 ± 0.7 cm) than NS (8.7 ± 1.4 cm) calves (P = 0.0398). However, mean allantoic fluid depth did not differ (P = 0.6120). There was a significant association between the body weight of calf and the diameter of the fetal aorta (P = 0.0115; r² = 0.3762). Surviving calves were lighter at birth (P = 0.0028) and were born later (P = 0.007) than NS calves. Calves born vaginally had a smaller fetal aorta (2.1 ± 0.1 cm vaginal and 2.4 ± 0.1 cm Cesarean) (P = 0.0487) and a lighter birth weight (41.4 ± 4.2 kg vaginal and 60.4 ± 2.1 kg Cesarean) (P = 0.0001) than calves born by Cesarean. Also, calves that underwent spontaneous labor (52.2% S and 0% NS; P = 0.0029) had a lighter birth weight (44.9 ± 3.8 kg) than calves that did not initiate labor (61.6 ± 2.2 kg) (P = 0.0004). Frequent ultrasonographic fetal monitoring allowed identification of differences between S and NS calves. Calves without a final decrease in FHR or with a large aortic diameter were more likely to require a Cesarean because of failure to initiate labor or fetomaternal disproportion. Parameters of fetal well-being and development during the last 3 weeks of gestation were first described in SCNT-derived beef calves.     

Correlations of SNHG5 genetic polymorphisms with susceptibility and prognosis to gastric cancer in a Chinese population

The most studied genetic polymorphisms associated with gastric cancer (GC) risk are located in protein-coding genes. However, these sited in long noncoding RNA (lncRNA) are not adequately explored yet. Here, we designed a case-control study of 848 cases and 880 controls to investigate the associations of polymorphisms (rs61396151, rs1059307, rs11961028, rs9351065) in lncRNA SNHG5 with the risk and prognosis of GC. The results indicate rs61396151 associated with decreased risk of GC (OR = 0.78, 95% CI = 0.62–0.96), but there were no correlations observed with the clinicopathological features of GC (P > 0.05). However, the CA genotype of rs61396151 was correlated with poor overall survival rate in a multivariate cox regression model (HR = 1.91, P = 0.040), but it was reversed with adjustment for age, gender and TNM stage (HR = 1.35, P = 0.213). Collectively, our results highlight the importance of SNHG5-related polymorphisms to GC susceptibility and prognosis.     

Investigating the relationship between lifestyle factors,family history,and diabetes mellitus in non-diabetic visitors to primary care centers

We investigated the risk levels associated with diabetes mellitus. They were assessed based on whether anyone in their family had a history of diabetes. The data collected are measurements of blood pressure, weight, height, and smoking habits, as well as physical activity and educational status. Based on the American Diabetes Association's (ADA) recommendations, the questionnaire included a diabetes risk assessment. The risk of diabetes was 76.3% among participants with a family history of diabetes. There is a 41.1% chance of diabetes among those participants whose fathers had diabetes, and a 39.3% chance of diabetes among those participants whose mothers had diabetes. Additionally, those participants who have siblings with diabetes were 24% at high risk for developing diabetes. The prevalence of the risk of having a family history of diabetes is higher in the women in the family (RR = 3.12; P = 0.0001) as compared to the men in the family (RR = 1.9; P = 0.0001). Risk of diabetes more in the male (1.13 times higher) in the current study based on the ADA scale. There is evidence that various factors, including lifestyle choices, physical attributes, and family history, influence the risk of developing diabetes in the current study. The results of the current study indicate that there is a strong association between patients with T2D and those who have a family history of diabetes. Considering Saudi Arabia's high diabetes risk, evidence-based lifestyle modifications are needed.     

Smoking Modifies the Associated Increased Risk of Future Cardiovascular Disease by Genetic Variation on Chromosome 9p21

Aims

Genetic predisposition for cardiovascular disease (CVD) is likely to be modified by environmental exposures. We tested if the associated risk of CVD and CVD-mortality by the single nucleotide polymorphism rs4977574 on chromosome 9p21 is modified by life-style factors.

Methods and results

A total of 24944 middle-aged subjects (62% females) from the population-based Malmö-Diet-and-Cancer-Cohort were genotyped. Smoking, education and physical activity-levels were recorded. Subjects were followed for 15 years for incidence of coronary artery disease (CAD; N = 2309), ischemic stroke (N = 1253) and CVD-mortality (N = 1156). Multiplicative interactions between rs4977574 and life-style factors on endpoints were tested in Cox-regression-models. We observed an interaction between rs4977574 and smoking on incident CAD (P = 0.035) and CVD-mortality (P = 0.012). The hazard ratios (HR) per risk allele of rs4977574 were highest in never smokers (N = 9642) for CAD (HR = 1.26; 95% CI 1.13–1.40; P<0.001) and for CVD-mortality (HR = 1.40; 95% CI 1.20–1.63; P<0.001), whereas the risk increase by rs4977574 was attenuated in current smokers (N = 7000) for both CAD (HR = 1.05; 95%CI 0.95–1.16; P = 0.326) and CVD-mortality (HR = 1.08; 95%CI 0.94–1.23; P = 0.270). A meta-analysis supported the finding that the associated increased risk of CAD by the risk-allele was attenuated in smokers. Neither education nor physical activity-levels modified the associated risk of CAD, ischemic stroke and CVD mortality conferred by rs4977574.

Conclusion

Smoking may modify the associated risk of CAD and CVD-mortality conferred by genetic variation on chromosome 9p21. Whether the observed attenuation of the genetic risk reflects a pathophysiological mechanism or is a result of smoking being such a strong risk-factor that it may eliminate the associated genetic effect, requires further investigation.     

Impact of meteorological factors and population density on COVID-19 pandemic in Saudi Arabia

Transmission and increase in cases and fatalities of coronavirus disease-2019 (COVID-19) are significantly influenced by the parameters of weather, human activities and population factors. However, study gap on the seasonality of COVID-19 and impact of environmental factors on the pandemic in Saudi Arabia is present. The main aim of the study is to evaluate the impact of environment on the COVID-19 pandemic. Data were analyzed from January 2020 to July 2021. The generalized estimating equation (GEE) was used to determine the effect of environmental variables on longitudinal outcomes. Spearman's rank correlation coefficient (r_s) was used to analyze the impact of different parameters on the outcome of the pandemic. Multiple sequence alignment was performed by using ClustalW. Vaccination and fatalities (r_s = ?0.85) had the highest association followed by vaccination with cases (r_s = ?0.81) and population density with the fatalities (r_s = 0.71). The growth rate had the highest correlation with sun hours (r_s = ?0.63). Isolates from variant of concern alpha and beta were detected. Most of the reference sequences in Saudi Arabia were closely related with B.1.427/429 variant. Clade GH (54%) was the most prevalent followed by O (27%), GR (9%), G (6%), and S (4%), respectively. Male to female patient ratio was 1.4:1. About 95% fatality and hospitalization were reported in patients aged >60 years. This study will create a comprehensive insight of the interaction of environmental factors and the pandemic and add knowledge on seasonality of COVID-19 in Saudi Arabia.     

Can amides be alternative cryoprotectors for the preservation of feline semen?

Sperm cryopreservation is a tool for the conservation of the genetic material of animals of genetic importance or for species preservation. In the case of domestic cats, this can be used to generate information about seminal harvest, evaluation and preservation, which is especially important due to its applicability to wild felids. This study evaluated seminal samples harvested by urethral catheterisation from 13 adult domestic cats. Samples were cryopreserved with experimental groups of extenders were defined by the penetrating cryoprotectant: 6% glycerol (GLY6%), 3% dimethylacetamide (DMA3%) and 3% dimethylformamide (DMF3%). The samples were thawed and evaluated by conventional microscopy and by computer-assisted sperm analysis (CASA). The structural and functional membrane integrity was assessed by supravital tests (EOS), hypoosmotic swelling tests (HOST) and flow cytometry (FC). There was a correlation (P < 0.05) between total motility and EOS (r = 0.54), HOST and FC (r = −0.62) and total motility and flow cytometry (r = 0.63), indicating that these are complementary parameters that increase the accuracy of the feline sperm quality evaluation post-thaw. The results regarding the structural and functional integrity of the sperm plasma membrane did not differ (P > 0.05) among groups. However, the DMA3% group had a lower (P < 0.05) percentage of morphological changes in the sperm tail compared to samples cryopreserved with GLY6% and DMF3%. Additionally, DMA3% provided lower values of immobile sperm post-thaw when compared to DMF3%. DMA is an interesting alternative to GLY and superior to DMF for the cryopreservation of feline semen at the studied concentrations.     

Evidence from genetic studies among rs2107538 variant in the CCL5 gene and Saudi patients diagnosed with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder that affects the adult population. Chemokines are proinflammatory cytokines that play a role in the development of chronic diseases such as obesity, gestational diabetes, and T2DM. The C-C Motif Chemokine Ligand 5 (CCL5) gene plays a role in antiviral immunity, tumor development, obesity, impaired glucose tolerance, and T2DM. This study aimed to investigate the genetic role of the rs2107538 variant in the CCL5 gene in Saudi patients with T2DM. Sixty subjects with T2DM patients and 60 healthy controls participated in this prospective case-control study. Prior to Sanger sequencing, genomic DNA was extracted and amplified with Polymerase chain reaction (PCR), after which the PCR products were purified. The collected data were used to conduct various statistical analyses to determine the relationship between T2DM and control subjects. The findings of the current study revealed a positive association for most parameters between T2DM and control subjects (p < 0.05). The frequency of genotypes (p = 0.002, AA vs.GG: p = 0.008, GA + AA vs. GG: p = 0.0002) and alleles (A vs. G: p = 0.0007) revealed a strong risk association. Multiple logistic regression with individual effects revealed a link between SBP and HDLc levels (p = 0.03). In patients with T2DM, waist (p = 0.001), TG (p = 0.0007), and LDLc (p = 0.0004) levels were all associated with the ANOVA. Finally, the rs2107538 variant was linked to an increased risk of T2DM in the Saudi Population. The GA and AA genotypes were strongly connected to the T2DM subjects. In order to rule out disease-causing variants in the global population, future research should use a large sample size.     

A Novel Method to Identify Routes of Hepatitis C Virus Transmission

Background

We propose a new approach based on genetic distances among viral strains to infer about risk exposures and location of transmission at population level.

Methods

We re-analysed 133 viral sequences obtained during a cross-sectional survey of 4020 subjects living in a hepatitis C virus (HCV) endemic area in 2002. A permutation test was used to analyze the correlation between matrices of genetic distances in the NS5b region of all pairwise combinations of the 133 viral strains and exposure status (jointly exposed or not) to several potential HCV risk factors.

Results

Compared to subjects who did not share the same characteristics or iatrogenic exposures, the median Kimura genetic distances of viral strains were significantly smaller between brothers and sisters (0.031 versus 0.102, P<0.001), mother and child (0.044 versus 0.102, P<0.001), father and child (0.045 versus 0.102, P<0.001), or subjects exposed to periodontal treatment (0.084 versus 0.102, P = 0.02). Conversely, viral strains were more divergent between subjects exposed to blood transfusions (0.216 versus 0.102, P = 0.04) or tooth filling or extraction (0.108, versus 0.097, P = 0.05), suggesting acquisition of the virus outside of the village.

Conclusion

This method provided insights on where infection took place (household, village) for several socio-demographic characteristics or iatrogenic procedures, information of great relevance for targeting prevention interventions. This method may have interesting applications for virologists and epidemiologists studying transmission networks in health-care facilities or among intravenous drug users.     

Clinical and pathological associations of the activating RAC1 P29S mutation in primary cutaneous melanoma

Activating mutations in the GTPase RAC1 are a recurrent event in cutaneous melanoma. We investigated the clinical and pathological associations of RAC1^P29S in a cohort of 814 primary cutaneous melanomas with known BRAF and NRAS mutation status. The RAC1^P29S mutation had a prevalence of 3.3% and was associated with increased thickness (OR=1.6 P = 0.001), increased mitotic rate (OR=1.3 P = 0.03), ulceration (OR=2.4 P = 0.04), nodular subtype (OR=3.4 P = 0.004), and nodal disease at diagnosis (OR=3.3 P = 0.006). BRAF mutant tumors were also associated with nodal metastases (OR=1.9 P = 0.004), despite being thinner at diagnosis than BRAF WT (median 1.2 mm versus 1.6 mm, P < 0.001). Immunohistochemical analysis of 51 melanomas revealed that 47% were immunoreactive for RAC1. Melanomas were more likely to show RAC1 immunoreactivity if they were BRAF mutant (OR=5.2 P = 0.01). RAC1 may therefore be important in regulating the early migration of BRAF mutant tumors. RAC1 mutations are infrequent in primary melanomas but may accelerate disease progression.