Aim & Objectives:
Creating a database comprising disease-causing mutations in genomic level, corresponding mRNA variants, related protein isoform as a product.
Overall Process plan:
We know that a mutation can be of several types and also it is random. But if a mutation in the gene level causes a change in the corresponding protein (as a change in amino acid residue due to change in triplet codon), then following post-translational modification the protein may function differently or lost its function as compared to its wild type.
Therefore, our idea is to create a database where we will be showing
1.The location of the mutation in the chromosome (as compared to the human genome mapping), the change in nucleotide from the original to the mutated one,
2.The corresponding mRNA variants due to the mutation [Note: Even one gene can form multiple mRNA variants due to the phenomenon called Exon Skipping].
Hence, it will be our target to find the possible mRNA variants from the given genetic mutation. This can be done by using an open web software called 'Mutalyzer'. There is a particular nomenclature called "Human Genome Variation Society (HGVS) Nomenclature" that is used to indicate a particular mutation in a chromosome, gene (DNA), mRNA and protein isoform level. Hence our target will be to find all the corresponding variants caused by the mutation and to list them in a table-like manner as we create the database.
List of Disease:
01 Achondroplasia
02 Huntington's disease
03 Marfan syndrome
04 Hereditary spherocytosis
05 Polycystic kidney disease
06 Familial hypercholesterolemia
07 Sickle cell anaemia
08 Cystic fibrosis
09 Tay–Sachs disease
10 Phenylketonuria
11 Galactosemia
12 Haemophilia
13 Duchenne muscular dystrophy
14 hereditary multiple exostoses
15 tuberous sclerosis
16 Von Willebrand disease
17 Albinism
18 Tay–Sachs disease
19 Niemann–Pick disease
20 spinal muscular atrophy
21 Roberts syndrome
22 Rett syndrome
23 Down syndrome
24 Turner syndrome
25 Aicardi syndrome
26 Edward syndrome
Details on each disorders:
Genetic Disorder ChromosomeAffected Gene Involved Type of Mutation Hereditary pattern
Achondroplasia 4 FGFR3 Gene alteration Autosomal Dominant
Huntington's disease 4 HTT Gene alteration Autosomal Dominant
Marfan syndrome 15 FBN1 Gene alteration Autosomal Dominant
Polycystic kidney disease1 16 PKD1 Gene alteration Autosomal Dominant
Polycystic kidney disease2 4 PKD2 Gene alteration Autosomal Dominant
Familial hypercholesterolemia 19 LDLRP1 Gene alteration Autosomal Recessive
Sickle cell anaemia 11 HBB Point mutation Autosomal Recessive
Cystic fibrosis 7 CFTR Gene alteration Autosomal Recessive
Tay–Sachs disease 15 HEXA Gene alteration Autosomal Recessive
Phenylketonuria 12 PAH Gene alteration Autosomal Recessive
Galactosemia 9 GALT Gene alteration Autosomal Recessive
Haemophilia X F8 Gene alteration X-linked Recessive
Duchenne muscular dystrophy X DMD Gene alteration X-linked Recessive
hereditary multiple exostoses 8,11,19 EXT1,EXT2,EXT3 Gene alteration Autosomal Dominant
tuberous sclerosis 9,16 TSC1,TSC2 Gene alteration Autosomal Dominant
Von Willebrand disease 12 VWF Gene alteration Autosomal Dominant
Albinism, oculocutaneous, type II 4 OCA2 Gene alteration Autosomal Recessive
Niemann–Pick disease 14 SMPD1 Gene alteration Autosomal Recessive
spinal muscular atrophy 5 SMN1 Gene alteration Autosomal Recessive
Roberts syndrome 8 ESCO2 Gene alteration Autosomal Recessive
Rett syndrome X MECP2 Gene alteration X-linked dominant
Down syndrome 21 - trisomy Not inherited
Turner syndrome X - Loss of chromosome Not inherited
Aicardi syndrome X unknown Gene alteration X-linked dominan
Edward syndrome 18 - trisomy Autosomal Recessive