The application of human pluripotent stem cells to model the neuronal and glial components of neurodevelopmental disorders.

Cellular models of neurodevelopmental disorders provide a valuable experimental system to uncover disease mechanisms and novel therapeutic strategies. The ability of induced pluripotent stem cells (iPSCs) to generate diverse brain cell types offers great potential to model several neurodevelopmental disorders. Further patient-derived iPSCs have the unique genetic and molecular signature of the affected individuals, which allows researchers to address limitations of transgenic behavioural models, as well as generate hypothesis-driven models to study disorder-relevant phenotypes at a cellular level. In this article, we review the extant literature that has used iPSC-based modelling to understand the neuronal and glial contributions to neurodevelopmental disorders including autism spectrum disorder (ASD), Rett syndrome, bipolar disorder (BP), and schizophrenia. For instance, several molecular candidates have been shown to influence cellular phenotypes in three-dimensional iPSC-based models of ASD patients. Delays in differentiation of astrocytes and morphological changes of neurons are associated with Rett syndrome. In the case of bipolar disorders and schizophrenia, patient-derived models helped to identify cellular phenotypes associated with neuronal deficits (e.g., excitability) and mutation-specific abnormalities in oligodendrocytes (e.g., CSPG4). Further we provide a critical review of the current limitations of this field and provide methodological suggestions to enhance future modelling efforts of neurodevelopmental disorders. Future developments in experimental design and methodology of disease modelling represent an exciting new avenue relevant to neurodevelopmental disorders.

Restriction fragment length polymorphism of HLA-DR and HLA-DQ allotypes in four endogamous groups of western India.

HLA-DR and HLA-DQ allele frequencies in four populations (Brahmin, Maratha, Gujarati Hindu Patel, and Parsi) of Bombay, western India, were analyzed using TaqI RFLPs detected by the cDNA probes DRB, DQB, and DQA. Although the overall differences in the HLA-DR and HLA-DQ genotype frequencies among the populations were not statistically significant, several population-specific haplotypes were significant. Multivariate analyses using data on 2 loci (HLA-DR and HLA-DQ) produced a meaningful pattern of genetic affinity and differentiation that parallels the analysis made when frequency data on 23 loci (21 blood group and protein loci and 2 class II antigen loci) are used. The RST for class II loci was 0.006; the genetic differentiation increased to 0.01 when data on 23 polymorphic loci were analyzed. The genetic affinity analysis shows the isolated nature of the Parsi and close genetic affinity between the two local populations of Bombay. Although the RFLP technique has several limitations compared with newly defined PCR-based methods, our analysis shows that the RFLP technique is still a useful adjunct method for studying HLA polymorphisms for which only limited data from the populations of the Indian subcontinent are available.