Question

Develop a case study/report on the Huntington disease and the gene for this disease is HTT gene. When you are developing the case study, start it from the DNA variant(a specific variant of the HTT gene) to the phenotype of the diseased patient.

The case report you should include the following:

. 1a) Transcript level coordinates of the variant if within mRNA (immature or mature)

1b) 5’-UTR, 3’, intron, exon, or splice site as examples

2c) If exonic, type of variant (SNP of CNV) and resultant changes in protein or protein level.

2) If the variant is in the non-coding region and if it involved in transcriptional regulation, and describe the proposed pathway.

Answer 1

1. Huntington disease is a brain disorder disease. This disorder in brain causes uncontrolled movements, emotional problems, and loss of thinking ability. Some of the symptoms are irritability, depression, poor coordination, and trouble to learn new information or making decisions. An infected person needs only one copy of the defective gene to develop the disorder i.e  one of the HTT gene is enough to cause the condition. This genetic disease is caused due to the repetitions of CAG nucleotides in the huntingtin (HTT) gene. The huntingtin gene also called as HTT or HD gene is the interesting transcript 15 gene, can codes aprotein called huntington protein. Due to its polymorphism, it can cause a various numbers of glutamine residues present in the protein. It contains 6-35 glutamine residues, so the mass is dependent on the number of glutamine residues present. Normal Huntington has 3144 amino acids in size and its protein is required for normal development before birth.

1b) The 5' end of the HD gene has three DNA base sequencing-- cytosine-adenine-guanine (CAG), coding for the amino acid glutamine repeatedly. The HD gene can be found on the short (p) arm of chromosome 4. Huntington can interact with other 19 proteins, 6 of them are for transcription, 4 for transport, 3 for cell signalling, and 6 others of unknown function. Huntingtin plays an important role in inhibition of mitochondrial electron transport. It also promotes oxidative damage to DNA. Cleavage and polyadenylation of mRNAs at the end of transcription might be a critical step in mRNA maturation, because choice of cleavage site depends on the transcription rate and the concentration of RNA binding proteins in the nucleus. mRNAs have multiple cleavage and polyadenylation sites that forms to mRNA isoforms of varying 3′UTR lengths,.

In order to find whether exon 1 of HTT mRNA  had spliced to exon 2, a series of RT-PCR assays on cDNA have been used.

The non coding RNAs  are known to mediate the regulation of gene expression. Non coding RNA (ncRNAs) play some critical roles in defining DNA methylation patterns, imprinting as well as chromatin remodeling, thus having a substantial effect in epigenetic signaling. ncRNAs can be divided into two groups based on an arbitrary threshold of 200 nucleotides --short (sncRNA) and long ncRNAs (IncRNA). sncRNAs involves in the transcriptional and translational regulation. The lnc RNAs are a group of large, heterogeneous ncRNAs of unknown function, it contains epigenetic marks indicating their ability to express differentially and introns in ln cRNAs emphasizes the existence of splice variants.