OMICS: Lect 15

Question 1

Human Genome Sequence

Answer 1

• determine entire seq of human genome.
• identify and map genes in human genome.
• find single nt polymorphisms.
• shows how few genes we have

Question 2

Annotation

Answer 2

-identifying the functions of open reading frame. 
Challenges: miss aspects of genome
-very small ORF
-small genes w/i larger genes
-genes on opposing DNA strands
-gene not translated into protein
-other unknown RNA species

Question 3

Why is it that chrom 13, 18 and 21 are only autosomes that can be found as trisomy and compatible w/ life?

Answer 3

• because size of chrom doesn’t always correlate w/ size by gene content. (Alt splicing ->resulting in many genes, RNA editing)
• these have the smallest gene content.

Question 4

Duplications in the genome

Answer 4

• 50% of genome is repetitive sequence.
• STR (di, tri or tetra) and VNTR (slightly longer repeats); highly polymorphic regions.
• Transposons (LINES and SINES “Alu element) -> most repetitive DNA in genome.
• Pseudogenes: vestigial, duplicated and processed pseudogenes.

Question 5

Pseudogenes

Answer 5

• Vestigial: now dormant. Ex: humans have the Vit C gene but it doesn’t function.
• Duplicated genes: not expressed. Ex: one of the globin genes in the B globin locus is not expressed.
• Processed pseudogenes: introns are removed from primary transcript by nl splicing, poly A tail added. Rev transcription and integration then yield a processed pseudogene which does not contain introns and has an A-rich tract at it’s 3’ end.

Question 6

Transposons leads to a disease by?

Answer 6

• integrating into a critical spot in a genome, disrupt a gene and cause disease.
• as repetitive sequence may lead to misalignment during meiosis and gene disruption.

Question 7

DNA fingerprinting

Answer 7

• may be used to settle paternity issues via PCR.

- use highly polymorphic single locus regions like STR or VNTR loci.

Question 8

Multiplex PCR:

Answer 8

an example of STR/VNTR PCR genotyping.

Question 9

Gene/chrom duplication or amplification occurs in a variety of ways:

Answer 9

• error in homologous recombination, retrotransposition event or duplication of an entire chrom.
• duplicated gene can evolve faster and the second copy of the gene is free from selective pressure.
• In a-thalessemia; due to repetitive struct of the a-cluster, deletions are the common disease causing mechanism for a-thal.

Question 10

Red-green color blindness?

Answer 10

explained by unequal intragenic recombination btwn a pair of X-chrom during meiosis.

Question 11

Chromosomal Microarray Analysis:

Answer 11

• can detect birth abnormalities.
• allows overview of the genome.
• > 1000s of probes immobilized on a solid support.

-CGH and SNP

Question 12

CGH

Answer 12

• comparing one genome to another.
• gives copy number variation
• important in pediatrics and diagnosis of developmental abnormalities.
• can detect smaller del or insertions than G-banding.
• diagnostic tool

Question 13

SNP chip

Answer 13

• single nucleotide polymorphisms
• may inform haplotype and pharmacogenomics.
• data collection tool

Question 14

Haplotype

Answer 14

• combination of alleles at different chromosomal loci that are transmitted together.
• HapMap describes common patterns of human genetic variation.

Question 15

Genome wide assoc. studies

Answer 15

• an attempt to uncover genetic determinants of multifactorial diseases (environmental and more than one genetic component)
• created by scanning 1000s of SNP
• search for genetic variations assoc w/ a particular disease.
  
  • > finding genetic variations that contribute to common, complex disease such as autism, asthma, cancer, diabetes type I/II, heart disease and mental illnesses.

Question 16

Transcriptome

Answer 16

• all mRNA in a particular cell under a particular condition.
• use of cDNA microarrays to determine the genes expressed
• allows comparison of expressed genes btwn nl and diseased states.

Question 17

Proteomics

Answer 17

• number of genes does not equal number of proteins because genes can have:
  1. multiple start sites
  2. alternate splicing
  3. RNA editing
  4. most proteins are modified (phosphorylation, glycosylation)

Question 18

At low pH,

At high pH,

At the isoelectric point

Answer 18

the protein has a +ve charge.

the protein has a -ve charge.

the protein has no net charge.

Question 19

Mass Spectrometry

Answer 19

• finds out what the identity of the protein is.
• fragments the protein w/ an electrical charge and then the mass is calculated.
• allows identification of minute amounts of a molecule.

Question 20

Epigenome

Answer 20

DNA methylation patterns on CpG repeats/islands are important in gene regulation.
-methylation of CpG islands are assoc. w/ reduced gene expression of nearby genes. (reduced expression of tumor suppressor genes)

Question 21

Fragile X

Answer 21

• result of excessive methylation pattern.
• expansion of a CGG repeat (CG gets methylated)
• reduced expression of FMR1 gene; leads to mental impairment.
• trinucleotide repeat disorder
• combo of genome duplication and epigenetic control