Sex influence on heredity

Question 1

Genetic phenomenon: Sex linked characters

Answer 1

sex influenced characteristics
sex limited characteristics
cytoplasmic inheritence (mitochondiral inheritence)
genetic maternal effect
genomic imprinting

Question 2

phenotype determined by

Answer 2

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

Question 3

Y linked inheritance

Answer 3

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)

Question 4

XD

Answer 4

XLHR- hypophasphatemia- Vitamin D resistant rickets

FMR1- fragile x syndrme

Question 5

XR

Answer 5

KAL1- kalmann syndrome

DMD duchenne muscular dystrophy

OTC ornithine transcaramylase deficiency

AIS androgen insensitivity syndrome

hEMA hemophila A

G6PD favism

Question 6

X-linked domainant inheritance

Answer 6

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

Question 7

Fragile X syndrome

Answer 7

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

Question 8

possible roles of FMRP

Answer 8

transporting mRNA and regulating synaptic protein synthesis, dendrite spine morphology

could be involved in the nuclear RNA interface patway

Question 9

Hypophasphatemia

Answer 9

vitamin D resistant rickets
phosphate deficiency: impaired bone mineralization

low blood level of phosphate

skeletal changes: slower body-growh

bending of the long bones

Question 10

mutation in hypophasphatemia

Answer 10

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

Question 11

XR characteristics

Answer 11

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

Question 12

Dystrophin

Answer 12

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

Question 13

Duchenne muscular dystrophy

Answer 13

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

Question 14

Becker muscular dystrophy

Answer 14

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

Question 15

mutations in dystrophin gene

Answer 15

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

Question 16

unieque of becker and duchene

Answer 16

allelic heterogenicity

same gene but dif phenotypes

Question 17

Hemophillia

Answer 17

XR
A- F8 mutation most common

B-F9 mutation

Question 18

Kallman syndrome

Answer 18

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

Question 19

KAL1

Answer 19

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.

Question 20

favism

Answer 20

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

Question 21

Hypohydrotic ectodermal dysplasia (HED)

Answer 21

Mutation of ectodysplasin A gene encodes EDA protein:Membrane protein
abnormal development of structures like skin, hair, nails, teeth, and sweat glands.

Question 22

sex influenced inheritance

Answer 22

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

Question 23

sex limited traits

Answer 23

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.

Question 24

puberty praecox

Answer 24

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

Question 25

homoplasmy

Answer 25

cytoplasm has either normal or mutant mitochondira

Question 26

heteroplasmy

Answer 26

cytoplasm has both normal and mutant mitochondria

Question 27

three parent babies

Answer 27

Three Parent In Vitro Fertilization (TPIVF)

offspring with three genetic parents, created through a specialized form ofin vitro fertilizationinvolvingcytoplasmic transferin which
the future baby’smitochondrial DNAcomes from a third party

Question 28

Genetic maternal effect

Answer 28

In the phenomenon of maternal effect, the genotype of the mother determines the phenotype of the offspring: usually due to substances present in the cytoplasm of the egg that determine the way the cytoplasm divides during early cleavage of the zygote.