Monday, February 11, 2019

Nucleic Acids, Genes, and Genomes

Be able to describe the basics of a eukaryotic protein coding gene - strands, exons, introns, promoter, UTR.

  • Strands- DNA is made up of two chains ("strands") of smaller building blocks called nucleotides. The strand that is used to transcribe an RNA molecule is called the template, or antisense, strand. The other strand is called the coding, or sense, strand. The coding strand has the same sequence as the new RNA, except that the coding strand of DNA has thymine where the new RNA has uracil.
  • Exons- Regions of the gene that will be translated into a protein.
  • Introns- Regions of the gene that lie between the exons.
  • Promoter- The region where transcription factors and RNA polymerase bind in order to begin transcription of an RNA molecule.
  • UTR- The untranslated region of a newly-produced mRNA molecule.

Have a basic understanding of a gene’s function.

A gene is a segment of DNA that includes a transcribed region and regulatory sequences. The transcribed region may code for a protein or RNA that has some function within the cell.

Describe the structure of monomeric units of nucleic acids - nucleotides. Understand the significance of DNA structure - antiparallel double helix.
Define the function of DNA & how genetic information is passed from DNA to RNA to proteins (The Central Dogma).
Know the basics of DNA & chromosome replication, transcription, translation, and codon chart use.
Be able to describe the different types of gene mutation at the DNA & protein level.
Be able to describe the different categories of DNA sequence within the human genome.

There are many different kinds of DNA sequences within the genome. While we often think of the DNA as the stuff that codes for proteins, in fact protein-coding regions only comprise a small percentage (~6%) of the genome. The rest is made up of regulatory sequences, unique noncoding DNA, and a whole load of repetitive DNA. Repetitive DNA sequences are critical in some disease processes (e.g. Huntington's Disease), and are useful for forensic purposes.

Define the different classes of DNA within the human genome.

I'm not really sure what we're supposed to know for this outcome. I know that there are different kinds of DNA, like A-DNA, B-DNA and Z-DNA, but since these didn't come up within the slides at all, I don't think we need to know what they are or what they do. The slides, however, do talk about orthologs and paralogs, so I'm going to talk about them here.

Orthologs and paralogs are homologous (similar) sequences that have derived from a common ancestor. Orthologs are similar sequences that can be found in different species that often have the same or identical functions. Paralogs are similar sequences that can be found within the same genome, and may be due to a gene becoming duplicated, and the duplicated gene gradually acquiring mutations. Paralogs may be different in their biochemical functions.

Understand the term pseudogenes and how they are derived within the human genome.

Pseudogenes are basically paralogs that have acquired deleterious mutations to the point where they are no longer functional. A different kind of pseudogene, called processed pseudogenes, lack a promoter and introns and are thought to derive from mRNA reverse-transcribed into cDNA (complementary DNA) and reintroduced into the genome (likely with the help of retroviruses, as humans lack the enzymes necessary for these processes).

Be able to describe the different types of repetitive sequence within the human genome.

As mentioned earlier, there are many repetitive DNA sequences within the genome. The two most common ones are minisatellites and microsatellites. Minisatellites, or Variable Number of Tandem Repeats (VNTRs) are 7-100 base pairs long, whereas microsatellites, or Simple Sequence Repeats (SSRs) are only 1-6 base pairs long.

The number of repeats can change during DNA replication due to a process called replication slippage. In replication slippage, the new strand of DNA that is being formed can sometimes come apart from the old DNA strand. When they re-anneal, they might not re-anneal correctly: the new strand may anneal to the next repeat of the sequence. Hence, when DNA replication continues, you eventually end up with the wrong number of repeats.

Understand the mechanism via which trinucleotide repeats cause human disease e.g. Huntington’s disease

Several human diseases are a result of trinucleotide repeats. Huntington's disease, for instance, is due to an expansion of CAG, which codes for glutamine, in the coding region of the Huntington gene. Since glutamine's one-letter symbol is Q, the polyglutamine tract that is formed is sometimes called a polyQ tract, and is thought to cause neurotoxic aggregates. The number of CAG repeats relates to the onset of the disease: people with fewer than 36 repeats do not have Huntington's disease, whereas people with more than 70 repeats have juvenile-onset Huntington's disease.

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