Trigger 9: Developmental disorders

Question 1

definition of DD

Answer 1

comprise a group of psychiatric conditions originating in childhood that involve serious impairment in different areas

Question 2

how many rare diseases

Answer 2

7,000

Question 3

how many rare diseases are genetic

Answer 3

80%

Question 4

how many rare diseases are in children

Answer 4

50%

Question 5

how many die before 5

Answer 5

30%

Question 6

individually DD are

Answer 6

rare

Question 7

collectively DD are

Answer 7

quite common

Question 8

molecular diagnosis is important for

Answer 8

• management
• treatment
• prognosis
• reproductive counselling

Question 9

most DD remain …. after standard NHS testing

Answer 9

undiagnosed

Question 10

why are most DD undiagnosed using standard NHS testing

Answer 10

• diverse clinical features

- diverse molecular causes and hinheritence

Question 11

why is DD described as an odyssey

Answer 11

due to the time and effort it takes to diagnose DD- often receiving diagnoses for them to be changed

Question 12

how many years on average does it take to diagnose a rate disease

Answer 12

4.8 years

Question 13

the longer it takes to diagnose

Answer 13

the more physicians patients see

Question 14

on average how many physicians do patients see in order to get a diagnosis

Answer 14

7.3

Question 15

variation in genetics may be

Answer 15

deleterious, neutral or beneficial

Question 16

most common mutations are (e.g. present in over 75%)

Answer 16

neutral

Question 17

most new mutations (which are very rare)

Answer 17

are deleterious

Question 18

how many base pairs of DNA (haploid- half)

Answer 18

3.6 billion

Question 19

how many base pairs in diploid genome

Answer 19

6 billion

Question 20

how many coding genes in the 3.6 bullion base pairs found in the haploid genome

Answer 20

20,000 coding genes (1-2% of genome)

Question 21

how many variants per individuals

Answer 21

4-5 million variants per individual

Question 22

majority of variants in genome are

Answer 22

Single nucleotide variants

Question 23

how many variants are rare variants

Answer 23

0.5 million (<5%)

Question 24

single nucleotide variants

Answer 24

a variation in a single nucleotide without any limitations of frequency

Question 25

how many base pairs involved in structural variation

Answer 25

20 million base paris

Question 26

how many variants in genes

Answer 26

20,000

Question 27

how many amino acid changing variants

Answer 27

10,000 (half of all 20,000 variants)

Question 28

how many loss of function variants within 20,000 variants in gene

Answer 28

100

Question 29

how many de novo mutations

Answer 29

70-120 (0-2 genes)

Question 30

sources of variation

Answer 30

exogenous and endogenous

Question 31

exogenous sources of variation

Answer 31

chemical agents e.g. smoking and UV radiation

Question 32

endogenous sources of variation

Answer 32

hydrolysis

deamination of methylated cytosine

base-pair mismatch during replication

Question 33

major classes of inheritence

Answer 33

• autosomal dominant (inherited or de novo)
• autosomal recessive
• X- linked

Question 34

autosomal genes

Answer 34

any genes on chromosome other than the sex chromosomes (X/Y)

Question 35

autosomal dominant

Answer 35

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

Question 36

autosomal recessive

Answer 36

autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop

Question 37

autosomal dominant are either

Answer 37

inherited or de novo

Question 38

de novo

Answer 38

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.

Question 39

X-linked disease

Answer 39

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,

Question 40

many genes still have

Answer 40

no known function

Question 41

mutations in around 4000 genes

Answer 41

know to cause disease

Question 42

what enables discovery of novel disease-causing variation in previously unclassified genes

Answer 42

genomic wide sequencing