Complex inheritance

Question 1

Non-Mendelian patterns of inheritance are

Answer 1

not predictable

Question 2

Types of non-Mendelian disorders

Answer 2

• de novo mutations
• mosaicism
• mitochondrial inheritance
• trinucleotide repeat disorders
• genomic imprinting disorders

Question 3

Most diseases are

Answer 3

polygenic

Question 4

De novo dominant diseases

Answer 4

are sporadic, no family history
caused by a new GERMLINE mutation (in parental gametes)
Inc+ risk with parental age
can be severe, esp. common in developmental disorders

Question 5

Mosaicism

Answer 5

presence of more than one genetic subtype in genetically related cells - only some cells express the phenotype (can be hard to diagnose because of this)
Two types:
1. Germline mosaicism in unaffected parent

2. Somatic mosaicism in child
   e. g. mosaic monosomy 7 (one copy=lethal, 2 copies severe developmental delay)

Question 6

Mitochondrial inheritance

Answer 6

maternal inheritance
genes essential for energy production
severity can be affected if there is heteroplasmy
e.g. MIDD (maternally inherited diabetes and deafness), LHON (leber hereditary optic neuropathy)

Question 7

Epigenetics

Answer 7

Heritable changes of DNA modification

rather than mutation of the DNA itself

Question 8

Heritable epigenetic changes can involve (3)

Answer 8

DNA methylation (at cytosine)
Histone modifications
ncRNA

Question 9

Genomic imprinting (epigenetics)

Answer 9

expression of gene is dependent on the parent of origin (e.g. mum’s is switched off and dad’s is on)

most genes are expressed from both alleles
a few are only expressed when inherited from one parent
methylation status depends on parent of origin

Question 10

Parent of origin effects

Answer 10

phenotypic effect depends on whether the allele is inherited from the mother or the father

e.g. prader wili, angelman

Question 11

Prader-wili

Answer 11

deleted paternal 15

obesity, diabetes, mental retardation

Question 12

Angelman

Answer 12

maternal deleted 15

mental retardation, petite, happy, hand flapping

Question 13

Multifactorial inheritance

Answer 13

the interaction between genetic and environmental factors
tend to cluster in families but incidence >5%
are ‘on a spectrum’ with genetics at one end and environment at the other

Question 14

Polygenic inheritance

Answer 14

due to genetic variation
involves many genes with small additive effects
e.g. asthma, diabetes, cancer

Question 15

Monogenic diseases can be (3)

Answer 15

autosomal dominant, autosomal recessive, or x linked

Question 16

autosomal dominant diseases can show

Answer 16

reduced penetrance

Question 17

trinucleotide repeat disorders can show

Answer 17

anticipation

Question 18

sex specific/parent of origin effects can be (3)

Answer 18

x linked, mitochondrial or imprinted

Question 19

common diseases have

Answer 19

complex polygenic inheritance