Sex influence on heredity Flashcards
Genetic phenomenon: Sex linked characters
sex influenced characteristics sex limited characteristics cytoplasmic inheritence (mitochondiral inheritence) genetic maternal effect genomic imprinting
phenotype determined by
genes located on sex chromosomes
genes in autosomes that are more readily expressed in one sex
autosomal genes whose expression is limited to one sex only
cytoplasmic gnees which are sually inherited entirely from only one parent
nuclear genotype of the maternal parent
genes whose expression is affected by the sex of the transmitting parent
Y linked inheritance
Only male to male transmission
An affected man’s father is affected (except new mutations)
All sons of an affected man are affected
Traits/symptoms manifest in every generation = VERTICAL PEDIGREE
Examples: SRY
Y-linked but not inheritable: Azoospermy (always new mutation)
XD
XLHR- hypophasphatemia- Vitamin D resistant rickets
FMR1- fragile x syndrme
XR
KAL1- kalmann syndrome
DMD duchenne muscular dystrophy
OTC ornithine transcaramylase deficiency
AIS androgen insensitivity syndrome
hEMA hemophila A
G6PD favism
X-linked domainant inheritance
Vertical
More affected females than males (no male to male transmission)
Most severe expression in homozygote (X’X’) females
Variable expressivity in heterozygote females (X’X) due to random X inactivation
Phenotype in heterozygote females is less severe than in hemizygote males (X’Y)
Some very rare genetic defects are lethal in males before birth
Fragile X syndrome
most common inherited mental retardation with variable penetrance and anticpation
trinucleotide repeat disease of CpG islands
more than 200 CGG repeats: CpG methylation the gene is transcriptionaly inactive
possible roles of FMRP
transporting mRNA and regulating synaptic protein synthesis, dendrite spine morphology
could be involved in the nuclear RNA interface patway
Hypophasphatemia
vitamin D resistant rickets
phosphate deficiency: impaired bone mineralization
low blood level of phosphate
skeletal changes: slower body-growh
bending of the long bones
mutation in hypophasphatemia
Gene and protein affected in problem: PHEX
Endopeptidase- role in the degradation of many moleucles– Phosphatonin moleucles
responsible for the bone mineralization
Affected in a way that the cells don’t reabsorb the phosphate groups— hyperphosphateuremia takes place, and hypophosphatemia in the blood
XR characteristics
horizontal pedigree
more affected males than females
males have one X – X-linked recessive diseases are expressed in hemizygotes (X’Y)
homozygote females (X’X’) are very rare (only in case of mild diseases) – most severe expression of disease
variable expressivity of X-linked diseases in heterozygotes (X’X)
due to random X inactivation
due to skewed X inactivation
Dystrophin
largest known gene 2.4Mb
Normal dystrophin: found in every cell because it is a connecting bridge between the membrane and the actin filaments that are found in every of the cells
Mutation will affect only the muscle cells
In the muscle cells the cytoskeletal actin and sarcolemma cannot bind normally – results in a rupture
Leaky membrane
Release some content from the muscle cells- creatinine kinase
Duchenne muscular dystrophy
1:3500 onset 3-5 years progressive proximal muscle weakness 9-13 y/o running no longer possible life expect: 15-20 years respiratory insufficency
Becker muscular dystrophy
1:20000 over 7 y/o progressive proximal muscle weekends 16-18 y/o cant run normal or reduced to 40 yers life expectance cardiomyophathy, resp insuf
mutations in dystrophin gene
Duchene:
large deletions 60%
duplications 5%
point mutations- mostly nonsense and frameshift
Becker:
large deletions 60%
duplications 5%
point mutations - mostly missense and splice mutations in frame
unieque of becker and duchene
allelic heterogenicity
same gene but dif phenotypes
Hemophillia
XR
A- F8 mutation most common
B-F9 mutation
Kallman syndrome
Hormonal deficiency
Anosmia or hyposmia occurs as a results of impaired development of the olfactory bulbs and olfactory nerves: no sense of smell
Hypogonadism results due to the reduced production of Gonadotropin-releasing hormone (GnRH).
Inheritance: X-linked recessive, autosomal dominant or autosomal recessive trait
KAL1
Normally there is an adhesion molecule: anosmin-1 which is expressed on neural cells
If mutation occurs, adhesion of those cells which lack this molecule will be abnormal
Those cells that normally migrate from the primary olfactory bulb to the hypothalamas – they cannot migrate then
Even patients with total anosmia can still detect certain volatile or strong aromatic compounds known as irritants. This is due to an alternative detection system, totally separate from the olfactory system mentioned above. At the back of the throat there are sensory cells linked to a cranial nerve called the trigeminal nerve which has a direct connection to the sensory centre of the brain. This system is totally unaffected in Kallmann syndrome.
favism
g6pd deficiency
ecogenetic disease
protective effect in P. falciparium infection
eating certain foods trigger it
problem- in pentose phosphate cycle glutation stays in oxized form
cannot reduce any oxidative agents
accumulation of peroxide in RBC
hemolysis, often severe and intravascular
symptoms jaundice
drugs: asprin, sulfanamide antimicrobials, certain antimalarials
Hypohydrotic ectodermal dysplasia (HED)
Mutation of ectodysplasin A gene encodes EDA protein:Membrane protein
abnormal development of structures like skin, hair, nails, teeth, and sweat glands.
sex influenced inheritance
Sex-influenced traits are inherited autosomally, but has higher penetrance in one sex than the other (e.g. pattern baldness is dominant in males, recessive in females).
The allele is dominant in one sex and recessive in the other
eg. the baldness: androgenetic alopecia:
Male Female \+/+ bald bald \+/- bald non bald -/- non bald non bald
sex limited traits
are inherited autosomally, but require specific hormones for expression. They are normally only expressed in either males or females. The genes for secondary sexual characters (e.g. breasts, beards) are sex-limited.
puberty praecox
AD
early puberty 5-6 years
elevated testosterone secretion
limited to male sex
receptor of luteinizing hormone is mutation so increased testosterone synthesis in absence of LH
both sex inherited, but disease appears only in men
