Trigger 9: Developmental disorders Flashcards
definition of DD
comprise a group of psychiatric conditions originating in childhood that involve serious impairment in different areas
how many rare diseases
7,000
how many rare diseases are genetic
80%
how many rare diseases are in children
50%
how many die before 5
30%
individually DD are
rare
collectively DD are
quite common
molecular diagnosis is important for
- management
- treatment
- prognosis
- reproductive counselling
most DD remain …. after standard NHS testing
undiagnosed
why are most DD undiagnosed using standard NHS testing
- diverse clinical features
- diverse molecular causes and hinheritence
why is DD described as an odyssey
due to the time and effort it takes to diagnose DD- often receiving diagnoses for them to be changed
how many years on average does it take to diagnose a rate disease
4.8 years
the longer it takes to diagnose
the more physicians patients see
on average how many physicians do patients see in order to get a diagnosis
7.3
variation in genetics may be
deleterious, neutral or beneficial
most common mutations are (e.g. present in over 75%)
neutral
most new mutations (which are very rare)
are deleterious
how many base pairs of DNA (haploid- half)
3.6 billion
how many base pairs in diploid genome
6 billion
how many coding genes in the 3.6 bullion base pairs found in the haploid genome
20,000 coding genes (1-2% of genome)
how many variants per individuals
4-5 million variants per individual
majority of variants in genome are
Single nucleotide variants
how many variants are rare variants
0.5 million (<5%)
single nucleotide variants
a variation in a single nucleotide without any limitations of frequency
how many base pairs involved in structural variation
20 million base paris
how many variants in genes
20,000
how many amino acid changing variants
10,000 (half of all 20,000 variants)
how many loss of function variants within 20,000 variants in gene
100
how many de novo mutations
70-120 (0-2 genes)
sources of variation
exogenous and endogenous
exogenous sources of variation
chemical agents e.g. smoking and UV radiation
endogenous sources of variation
hydrolysis
deamination of methylated cytosine
base-pair mismatch during replication
major classes of inheritence
- autosomal dominant (inherited or de novo)
- autosomal recessive
- X- linked
autosomal genes
any genes on chromosome other than the sex chromosomes (X/Y)
autosomal dominant
the effect on phenotype of one allele masks the contribution of a second allele at the same locus
- if you get the abnormal gene from only one parent, you can get the disease
autosomal recessive
autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop
autosomal dominant are either
inherited or de novo
de novo
A genetic alteration that is present for the first time in one family member as a result of a variant (or mutation) in a germ cell (egg or sperm) of one of the parents, or a variant that arises in the fertilized egg itself during early embryogenesis.
X-linked disease
a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males (who are necessarily hemizygous for the gene mutation because they have one X and one Y chromosome) and in females who are homozygous for the gene mutation,
many genes still have
no known function
mutations in around 4000 genes
know to cause disease
what enables discovery of novel disease-causing variation in previously unclassified genes
genomic wide sequencing
