Single Gene Pathology Flashcards
what are genome browsers
provide a reference genome to compare with those that contain pathogenic genes
what is contained within genome browsers
ideogram - chromosome diagram genes at their loci OMIM genes - genes with associated diseases comparison to other organisms repeat sequences
what are the two main causes of single gene pathologies
repeat sequences and point mutations
what are the repeat sequences divided into
LINE (long interspersed nuclear element) eg LINE1 - small minority active (promote their own mobility by retrotransposition)
Alu (SINE - short interspersed nuclear element) primate specific unlike LINE1
dependant on LINE1 for retrotransposition
give an example of a single gene pathology caused by repeat sequences
Haemophilia A
LINE1 elements inserted into factor 8 gene causing it to become non-functional
what is a chiasm in repeat sequences
crossing over of chromosomes in meiosis
lots of repeats lead to misalignments causing unequal crossing over
gives some examples of diseases caused by chiasm
DiGeorge syndrome (chromosome 22) and williams [microdeletion affecting ELN gene - elastin] (large scale duplications or deletions)
PMP22 - hereditary neuropathy with pressure palsies
duchenne MD - duplication or deletion
why can deletions of exons very in pathological severity
if exon deletion causes frameshift all following exons are incorrectly read
what is a point mutation
most common type of single gene pathology
single nucleotide substitutions
what are the types of point mutations
silent
missense - conservative or non conservative
non-sense
what are the types of missense point mutation
change in amino acid
conservative - swap amino acid with similar properties (less effect)
non-conservative - swap with difference property amino acids
what are the amino acids types ordered into
acidic - Glu, Asp Basic - lys arg polar - Ser, Thr, Aún, Gln, Ser, His non-polar - Ala, val, leu, Ill, Met, aromatic, Phe, Tyr, Trp, His other - gly pro
what is non-sense point mutation
truncated protein produced (shortened)
describe hyper mutability of CG dinucelotides
CG often methylated after replication which is very smiler to thymine so common for there to be CG - TG mutation (1/3 pathogenic mutations)
what does a mutation in GT cause
splicing defect as splicing proteins can’t recognise splice site - GT almost always signifies end of an exon
during mutation nomenclature what are the three reference sequences
genomic DNA = g
cDNA = c
protein = p
what does “>” mean
changed to
what are deletions or insertions named as
del or ins
what is a * used for
symbolise stop codon
what is the difference in function of genes between dominant and recessive inheritance
dom - often results in gain or alteration rather than loss of function
rec - results in loss fo function
what is a trinucelotide repeat expansion
repeat expansion can cause disease
change in the number of triple repeats
what disease is caused by polyglutamine repeats
CAG
neurodegenerative disorders such as Huntington’s or spinocerebellar ataxis
what disease are caused by repeat expansion of anon-coding genes
fragile X syndrome
myotonic dystrophy
what is huntington’s disease
neurodegen - cognitive loss, neuronal loss in corpus striatum and cortex, psychiatry changes, invol movement
autosomal dominate - heterozygous CAG repeats
anticipation and mutational instability
what is fragile X
X linked so males severely affects, females less so
large ears, testes
strange inheritance, repeat expansion only changes when passed on maternally
