T1: Genome anatomy Flashcards
How long is the human genome?
3x10^9 Nucleotides long - a small amount is epigenetic information
How is the human genome laid out?
DNA is directional. DNA and RNA are synthesised in 5’-3’ direction. DNA runs in double anti-parallel strands. For a gene, the “sense” strand is the one that is written and ends up in mRNA after transcription.
Chromosomes are the packages in which DNA is wrapped up. A nucleosome is formed with around 200 bp of double stranded DNA wrapped around an octamer of histones. Parts of the histones interact with the DNA in a specific way. Modification of the histones is how the epigenetic information is stored.
Over 90% of our DNA is non-coding. We have about 20,000 protein-coding genes. There is a size discrepancy between the gene and the mRNA.
How is DNA replicated and disease inherited?
Semi-conservative replication. It is inherited through the fusion of the gametes. The overall process of DNA replication remains to stay quite accurate. Exons make up only 2% of the genome. This means there is a reduced chance of these errors being in the coding areas.
New mutations not found in the parents, are only found in a small amount of disease. The majority of new mutations (de novo) that cause genetic disease come from the father. This is most likely due to the fact most new mutations come from replication errors. The more cell divisions before you produce a gamete, the greater the chance of mutation. More replication occur in spermatogenesis than in the production of oocytes. Older fathers, due to the greater number of cell divisions, has a greater effect on mutations. More genetic areas accumulate. Replication areas causing single base mutation is usually caused by the father. There are also risks for older mothers, in terms meiotic errors.
Rare disease that result from germline mutations (due to inheritance from a gamete and so are in every cell) occur during gametogenesis. A replication error that occur in sematic cells have different consequences. This is not passed down.
What is a karyotype?
All of the chromosomes of an individual laid out in size order.
What is haploinsufficency?
Haploinsufficent - genes that do not tolerate a loss of one copy
We cannot tolerate the loss of one autosomal chromosomes.
The exception is the X chromosome as there is dosage compensation.
What are pseudoautosomal regions?
Psuedoautosomal regions - these are homologous in the X and Y chromosomes. They do exchange genes during mitosis. Most of the chromosomes however on the X chromosomes are X-unique and so the gene number is n = 1 in males (hemizygous state).
What is the Y chromosome mostly made out of?
The Y chromosome is mainly repetitive mostly heterochromatin DNA. There are very unique genes on the Y chromosome, the most important is SRY which causes the development of the testis.
What is the difference between heterochromatin and euchromatin?
The major difference between heterochromatin and euchromatin is that heterochromatin is such part of the chromosomes, which is a firmly packed form and are genetically inactive, while euchromatin is an uncoiled (loosely) packed form of chromatin and are genetically active.
What is the difference between mitochondrial DNA and nuclear DNA?
Mitochondrial DNA is single stranded unlike the double stranded nuclear DNA. It contains codes for enzymes involved in oxidative phosphorylation. The DNA is circular rather than linear like that found in the nucleus. Mitochondrial DNA are passed down in the cytoplasm in the oocyte.
What are the different sequence classes in the human genome?
- Single-copy sequence (non-repetitive).
2. Repetitive sequences. This can be either satellite DNA or interspersed repeats.
What is alternative splicing? Give 2 examples.
One gene can cause more than one protein through using the exons in different combinations. If there are 4 exons, you can get different splicing.
This can be mutually exclusive splicing and exon skipping.
What are pseudogenes?
Divergence occurs through mutation. Some duplicated copies if no longer under selective pressure accumulate mutations that make it inactive. These are called pseudogenes.
What are processed genes?
A processed genes is a intron less copy of a gene. Usually located in a remote location form the gene. Reverse transcription and reintegration (this is part of the normal lifecycle of viruses). Theses occasionally remain function such as the PGK2 gene. Most are non-functional. There is often a remnant of the mRNA poly A tail at the end of the reintegrated gene.
What is alphoid DNA?
The alphoid DNA is a type of satellite DNA found at the centromere. T
What are intersepersed repeats?
A type of repetitive sequence. They are scattered around the DNA. Individual copies are present at many locations, maybe within or between or part of genes. Alu repeat is one member of a larger family of repeats called SINES. 5% of the gene is made of Alu repeated.
