Systems to cells Flashcards
Who are the Nijmegen family?
This was a family that went through pedigree analyses in 1993. This was to try and understand why some males in the family showed inappropriate behavior such arson or assault.
What did analysis of this family first reveal about the aggressive members?
All aggressive members were male, 8/23 males in the family were aggressive. All the affected were genetically related, not just by marriage. This suggests the condition was X-linked.
What mechanism was used to narrow down the gene that may be causing this?
There are around 1000 genes on the X-chromosome. Gene mapping using short tandem repeats was used. Tandem repeats are DNA sequences that are repeated variably across the population. No phenotypic effect.
How can STRs be used to map a chromosome?
Researchers can look at whether to aggressive phenotype is co-inherited with with STRs. The nearest STRs to the gene will be inherited 100% of the time, while further away genes will be inherited 50% of the time. Two STRs were co-inherited with inappropriate aggression- the gene for inappropriate aggression must be in that region.
How can a the correct gene be identified once the region has been found?
The candidate gene approach can be used, a gene that may plausibly cause the mutant phenotype we observe.
What two genes were the best candidates for inappropriate aggression?
Monoamine Oxidase-A and Monoamine Oxidase-B. There function is the to metabolize excess neurotransmitters, which effectively calms the fight or flight response. The role of these genes was to calm the body down after the spike in adrenaline from the fight or flight response.
What type of mutation was the inappropriate aggression.
Recessive, loss of function mutation. Mutants will still be in fight or flight stage for a longer period after the incident as calm down mechanism is mutated.
What differed between the two Monoamine Oxidase genes?
They have an identical intron and exon structure and lie head to tail next to each other. This suggests one of the genes was duplicated in evolutionary history: paralog. The amino acids in the genes are 70% identical, but MOXA c85% and MOXB c15% of the activity. They both metabolize serotonin, dopamine and noradrenaline.
How was the mutated gene found?
Urine samples were taken from the family. Affected males had no MOXA activity in their urine while females did. MOXB activity was normal across the whole family.
Researches looked at SNPs to analyze the amino acids produced, what did this uncover?
At C936T, the T was unique to some of the family members and this coded for a premature stop codon.
How can MOXA affect be studied experimentally through mouse models?
Mice have essentially the same genes as humans, they have MOXA and MOXB on the X-chromosome. Researchers made a partial deletion on the MOXA gene and observed aggressive behavior during and intruder test. Instead of holding an aggressive stance, mutant mouse attacks the intruder.
How can MOXA affect be studied in Rhesus monkeys?
There is a natural polymorphism of the MOXA gene in monkeys which results in 75% if the normal MOXA levels. This is due to a variable region upstream of the start codon, 5-6 repeats are normal, 7 repeat monkeys show antisocial behavior.
How long did the first genome sequence take?
First DNA sequence took 13 years to do and took worldwide collaboration
How have oxford nanopores changed DNA sequencing?
They have made DNA sequencing very quick and relatively cheap (£600-£1000)
Who is James Renwick?
He was an early developer of gene mapping. He figured out that everyone in a family that had nail patella syndrome had ABO blood group. Co-inheritance allowed hi, to assign this gene to a chromosome.
