ibrahim-olajide.github.io

Advice

This is merely a repository of a project under study and preparation for publication.

Variation in Genes caused by Mutation and Alternative Splicing : Identification and Characterization of Pathogenic Variants in TRY, OCA2, HPS-1 and OA1 Genes that leads to Albinism

• Albinism is a group of genetic conditions in which a person has no or very little melanin pigment in their skin, hair and eyes. Albinism occurs in all racial and ethnic groups throughout the world. In Australia, about 1 in 17,000 people have some type of albinism.
• The genes for albinism are passed down from both parents, who may not be directly affected by it themselves. However, there is no simple test to determine whether a person carries a gene for albinism.

There are 2 main types of albinism:

• Oculocutaneous albinism: in which the hair, skin and eyes are all affected
• Ocular albinism: which is much less common, and involves only the eyes. The skin and hair colour appears similar to that of family members There are also some extremely rare conditions where people have albinism and other health problems. Examples are Hermansky Pudlak syndrome, Chediak Higashi syndrome and Griscelli syndrome.

Signs and Symptoms of Albinism:

Some children with albinism are born with pinkish-white skin and white hair. Their eyes are usually light grey, blue or hazel, although they can look pink in the light.

OCULAR ALBINISM TYPE1:

• Ocular albinism type 1 (OA1) is an X-linked disorder characterized by severe impairment of visual acuity, retinal hypopigmentation and the presence of macromelanosomes. We isolated a novel transcript from the OA1 critical region in Xp22.3-22.2 which is expressed at high levels in RNA samples from retina, including the retinal pigment epithelium, and from melanoma. This gene encodes a protein of 424 amino acids displaying several putative transmembrane domains and sharing no similarities with previously identified molecules. Five intragenic deletions and a 2 bp insertion resulting in a premature stop codon were identified from DNA analysis of patients with OA1, indicating that we have identified the OA1 gene.

OCULOCULAR ALBINISM:

• Oculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most common causative genes in non-syndromic OCA are TYR and OCA2 and HSP1 is in the syndromic albinism. People with albinism usually have poor vision. Glasses can help, but some have poor vision even with glasses. Several eye conditions can affect people with albinism including nystagmus, which is horizontal back and forth movement of the eyes, and photophobia, which is sensitivity to bright light and glare.

PROCEDURE

• All the the variants of OCA1,OCA2,HPS-1 and OA1 and isoforms (translated proteins) from each variants were aligned for variant calling using Clustal W software.
• ORF finder was used to determine the frame and the particular gene responsible for the expression was also determined.

TOOL/ PIPELINE/ SOFTWARE USED

• BLAST, ORF-Finder
• BioEdit, Clustal Omega, ClustalW, MEGGA,MAFFT
• GALAXY
• Mitoswebser, Genome Data Viewe
• Cytoscape,DAVID,STRING, and GEO2R

ANALYSIS

• Gene Expression Profiling: To compare and analyse data on Gene Expression Omnibus (GEO) Pipeline/Webtool- GEO2R

• Functional Enrichment:Gene Ontology (Biological process, Cellular Component and Molecular Function)

  Pipeline/Webtool- DAVID

• Network Analysis: For gene-gene interaction and disease prediction

  Pipeline/Webtool- STRING and Cytoscape

CONCLUSIONS

• Alternative splicing of gene is one of the key contributors to gene mutation which has become threat to life of people, even for the entirety of their lifetime. To treat OCA, gene therapy has shown important improvements in animal models. This technique can increase melanin production in the OCA. For this purpose, gene correction techniques are already available. These comprise techniques to edit erroneous segments in the genes such as TYR gene and LRMDA gene. This technique can include gene delivery vectors and gene editing tools. Gene delivery vectors may include such as retrovirus, adenovirus and AAV. Gene editing tools may comprise such as TALENs system and CRISPR/Cas9 system. For example, CRISPR/Cas9 system can correct albinism phenotype in rats. Either TALENs or CRISPR/Cas9 system in combination with iPSCs can be useful to fight albinism. It seems that gene therapy would be very beneficial for treating OCA disorder.

Subsequent Analysis (Under Study)

• Exploring the link between each variant gene and screening the key genes using in silico analysis

REFERENCES

• Journal of Advances in Biology & Biotechnology, 16(3): 1-12, 2017. DOI:10.9734/JABB/2017/38504
• https://pubmed.ncbi.nlm.nih.gov/35328057/