Moyzis2-human genome

Question 1

What are some characteristics of the human genome?

Answer 1

• 3000Mb, 1.5% protein coding, 50% repetitive, 6.6% heterochromatin, 3% highly conserved w/ unknown function
• 25K genes, 9 exons (122bp) in average gene,
• 500aa for average polypeptide
• Many genes have multiple copies
• Exons are short, introns are long
• genes up to 2500kb, dystrophin

Question 2

Why is there alternative splicing?

Answer 2

• Ability to make more proteins (generate more than 30K proteins, 50% of unknown function)
• Cold also be used as a regulatory/checking mechanism
• Creates diversity from a single gene

Question 3

What is the importance of NF1 gene?

Answer 3

• Mutations or deletions lead to neurofibromatosis

- Gene has genes within itself

Question 4

What is repetitive DNA?

Answer 4

Accounts for 50% of genome:

1) Tandem repeats (centromeres and telomeres)
2) Interspersed repeats (“molecular parasites,” Alu and Line1), account for 20% of genome.

Question 5

Why is the human genome sequence incomplete?

Answer 5

Because centromeric DNA is too difficult to clone. Various tandem repetitive sequences are present.

Question 6

What is dyskeratosis congenita?

Answer 6

• Mutation of RNA component of telomerase
• defects in rapidly-dividing tissues
• Cirrhosis, gut problems, alopecia, fibrosis, failure to produce blood cells, hypogonadism

Question 7

Explain the interspersed repeats:

Answer 7

• Alu: 300 bp, 10^6 copies
• Line1 (L1): 7Kb, 10^5 copies
• Both are retroposons (move tru RT mechanism)
• Most copies are transcriptionally inactive
• Internal Pol III promoter
• They help patch DBS breaks
• L1 RT make copies of any genes, pseudogenes
• Movement of transposons: source of mutations
• VJ rejoining evolved from a transposon recombinase

Question 8

What is genomic imprinting?

Answer 8

Maternal or Paternal allele silenced. DNA modified by methylation, but “reset” in the
germ line. 10% of human genes are imprinted.

Question 9

What is PWS and AS?

Answer 9

• Same DNA deletion results in two different disorders if inherited from mothers or fathers:
  1) Prader Willi syndrome, paternal defective gene
  2) Angelman syndrome, maternal defective gene
• Neuro-genetic disorder characterized by severe intellectual & developmental disability, sleep disturbance, seizures, jerky movements, happy demeanor.

Question 10

What are alleles and SNPs?

Answer 10

• Allele: variation in the “spelling” of a gene

- SNP: single nucleotide polymorphism, the most common type of allelic variation

Question 11

What is Alu and L1?

Answer 11

Two type sof interspersed repeats:

• > Alu: 300bp, 10^6 copies, retrosposons
• > L1 (lines): 7Kb, 10^5
• > RT mechanism to move from point to point in the genome. They have an internal Pol III promoter.

Question 12

What is a possible way to cure Thalessemia?

Answer 12

To reactivate the fetal globin gene to replace the defective adult globin.

Question 13

What are the types of alternate splicing?

Answer 13

• Cassette exon
• Mutually exclusive exons
• Intron retention
• Alternative 5’ or 3’’ splice sites
• Alternative promoters