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التحري عن الطفرات في جيني CNTNAP2 وIL1RAPL1 في مرضى التوحد == Mutation Screening of CNTNAP2 And IL1RAPL1 Genes In Autistic Patients
Author name:
بشير كاظم خرميط
Supervisor name:
عبد الكريم عبد الرزاق القزاز
General topic:
Biology
Specific topic:
Biotechnologies
Degree:
Master
University:
University of Baghdad - College Of Science - Department Of Biotechnology
Language:
English
University location:
Baghdad
First pages:
24T2855 - p.pdf
Abstract:
ان اضطرابات طيف التوحد هي مجموعة من الظروف التي تتميز بضعف في التواصل الاجتماعي ونمطية في السلوك. يختلف الاشخاص المتوحدين اختلافا كبيرا في التطور المعرفي والتي يمكن ان تتراوح من فوق المتوسط الى العجز في التفكير. رغم ان اضطرابات طيف التوحد هي تورث بشكل كبي | The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviors. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability (ID). While ASDs are known to be highly heritable (~90%), the underlying genetic determinants are still largely unknown. The research studies correlate between Contactin - associated Protein - Like 2 (CNTNAP2), Interleukin - 1 Receptor Accessory Protein - Like1 (IL1RAPL1) genes and ASDs. This study includes forty autistic patients and forty non autistic children as control groups (twenty unaffected sibling and twenty unrelated children). The age of autistic and non autistic children was ranged from 3 to 10 years. Blood samples of autistic patients were collected from Rahman specialist centre for the care and service autistic children in Baghdad. DNA was extracted from blood samples for molecular detection of CNTNAP2 and IL1RAPL1 mutations associated with ASDs by the use Polymerase Chain Reaction (PCR) technique and sequence analysis. PCR reaction was performed to amplify exons (14, 17 and 20) of CNTNAP2 gene that encode to CASPR2, a member of the neurexin family which functions in the nervous system as cell adhesion molecules and receptors. The PCR results revealed that identical bands related to the CNTNAP2 exons were present in all samples. Therefore, five samples (four from autistic patients and one from control sibling) were selected for genotype analysis of CNTNAP2 exons (14, 17 and 20) by direct sequencing. Genotype analysis revealed that there were no any variants in CNTNAP2 exons, but it shows that four different mutations were identified in non coding region (introns) of the CNTNAP2 gene. These mutations were seen only in autistic patients but absent in control sample. Three of these mutations are single nucleotide polymorphisms (SNPs) (rs3779031 A/G in 2118282 position, rs3779032 A/C in 2118436 position and T/G in 2117905 position). The other mutations were deletion in one nucleotide (Del A/ - in 2117901 position). SNP rs3779032 A/C are located at intron 21 while other mutations are located at intron 19. The current study showed that two common SNPs (rs3779031 and rs3779032) in CNTNAP2 were strongly associated with ASDs, where the frequencies of these SNPs were relatively high. SNP rs3779031 identified in two autistic patients while rs3779032 identified in three autistic patients from four unrelated families with ASDs. PCR reaction also was performed to amplify exons (3, 4, 5, 6, 7, 8 and 9) of IL1RAPL1, a gene implicated in calcium - regulated vesicle release and dendrite differentiation. The PCR results show a large intrgenic deletion (Deletion of exons 3 and 4) in six autistic patients, two of these patients were twin. This deletion may be incomplete penetrance due to phenotypic heterogeneity of these patients. This study provides evidence of the role of genetic factors in the etiology of ASD and the important CNTNAP2 and IL1RAPL1 genes mutation of pathogencity ASDs.
