Autosomal and X-linked disease (dom and rec) Flashcards
What does sickle cell protect against and how?
Malaria
atypical can’t retain parasite
heterozygote = advantage
what does Phenylketonuria protect against?
fungal infections in fetuses
elevated Phenylalanine inactivates toxin
What does Cystic fibrosis protect against? How?
Diarrheal disease (cholera and typhoid fever)
fewer cl prevents water loss in intestinal cells.
What are the Autosomal dominant diseases?
(growth)
Achondroplasia and hypochondroplasia
(neurological Repeat disorders)
Huntington’s Disease
Myotonic dystrophy
(tumour supression)
retinoblastoma
neurofibromatosis
what are the autosomal recessive diseases?
(membrane)
Cystic fibrosis
(metabolic)
PKU
(Blood)
Sickle Cell
Haemachromotosis
thalassemia
Anticipation in Huntington’s disease
more common in Paternal transmission
from the instability of the CAG repeat in spermatogenesis
What are the X-linked recessive disorders?
Colour vision deficnecy
DM Dystrophy
Kennedy’s Disease
Haemophilia
What is a X-linked dominant disorder?
Hypophosphatemic Rickets
What is the affected gene and normal action of this gene for PKU?
what is the common mutation?
PAH gene
makes phenylalanine hydroxylase = process phenylalanine which is building block of proteins
Arg408Trp
Clinical features of PKU
Early
-vomiting
-irritability
-mousy odour to urine
-eczema like rash
Nervous
-hypotonia
-more active reflexes
untreated
-microcephaly
-widely spaced teeth
-prominent cheek and upper jaw bones
What is the affected gene and normal action of this gene for Thalassemia?
HBA 1 and 2 (a) and HBB (b)
incorrect synthesis of a or b globin chain
Types of a-thalassemia (symp and treatments)
silent
-1/4 mutated
-asymptomatic
minor
-2/4 mutated
-mild anaemia
HbH
3/4 mutated
-mild-mod anaemia
-enlarged spleen
-treated with transfusion
Hb Barts
-4/4 mutated
-severe anemia
-excess fluid build up
-not survive after birth
Types of b-thalassemia (symp and treatments)
Minor
1 of 2
- lifelong mild anemia
intermediate
2 of 2 mutated
- mild-mod anemia, slow growth
-splenectomy, blood transfusion and folic acid supplementation
major
-2 0f 2 affected
-life-threatening anemia in the first year
-jaundice
enlarged spleen and bone changes
-bone marrow transplant and regular transfusions
potential for gene therapy (haemoglobin switching)
What is the affected gene and normal action of this gene for Sickle Cell anemia?
what is the common mutation?
HbA gene: adult form of hemoglobin. mutation causes changed fibre formation and disorder RBC shape
HbA–> HbS
mutation
DNA: CTG –> CAG
RNA: GAG –> GUG
Clinical features of Sickle Cell
protection aganist malaria (Heterozygte advantage)
Intense pain in various parts of the body, often in the bones, joints, abdomen, or chest
Fatigue, shortness of breath, and paleness
What is the affected gene and normal action of this gene for Haemochromatosis?
what is the common mutation?
HFE gene
mutant= cannot bind to transferrin receptor that regulates Hepcidin (iron) = EXCESSIVE absorption of iron
mutation: p.cys282Tyr or p.His63ASP
Clinical features of Haemochromatosis
impacts the ability to absorb protein (stored in tissues instead)
joint pain
fatigue
bronze pigment
abdominal pain
decreased libido
often later diagnosis in females due to menstartion (iron removal downplays affect of high iron)
What is the affected gene and normal action of this gene for Cystic Fibrosis?
what is the common mutation?
CFTR
Chloride ion channel = maintains epithelial surface hydration, regulates luminal pH and has significant role in salt absorption
Phe508(del) = misfolded protein so protein does not migrate to cell membrane
Clinical features of cystic fibrosis.
Pancreas
-blocked glands
-cyst formations
-decreased fat digestive enzymes
lungs
-mucus thicker = persistent cough and infections
reproductive ducts
-ductus deferens blocked= infertile
sweat glands
- no re-uptake of secreted salt = salty skin
What is the affected gene and mechanical actionof mutated gene for Achondroplasia Hypochondroplasia?
FGFR3 = codes for a TKR responsible for signalling growth = limits bone formation
gain-of-function = (hypermorphic –> receptor constitutively active)
-inhibits chondrocytes and endochondral ossification
de novo - common cause of mutation
what is the most common mutation for Hypochondroplasia and Achondroplasia respectively?
H= P.Asn540Lys
A= p.Gly380Arg
Clinical features of achondroplasia
- Abnormal bone growth → short stature with disproportionately short arms and legs
- large head and prominent forehead
- trident hands
- delayed motor development
- intelligence and life span normal
Clinical features of Hypochondroplasia
- normal birth weight and length
- disproportion in limb trunk length (mild and easily overlooked during infancy)
- typically present as toddlers or school-aged children with failure to grow
- short stature with disproportionate limbs as they age
Achondroplasia vs Hypochondroplasia
Severity: A= higher risk of complications
Stature: A= severe drawftism and DISproportionate stature, H= Proportionate stature and mild drawftism
head: A= large, H= normal
Huntington’s disease clinical features
progressive motor disability featuring chorea
cognitive decline
mental distrubances
changes in personality/ depression
What is the affected gene and normal action of this gene for Huntingtons?
what is the common mutation?
HTT
normal
-important in neurons and brain development before birth
mutation
Glutamine (CAG) repeats (over 40 for penetrance)
HTT protein aggregation in cells of caudate nucleus = cell atrophy and death
paternal transmission = anticipation
What is the potential treatment option for autosomal dominant diseases?
siRNA interference
What is the affected gene and normal action of this gene for Myotonic Dystrophy?
what is the common mutation?
DMPK gene = instructions for making myotonic dystrophy protein kinase = ole in muscle, heart, and brain cells
> 37 CTG repeats
can chow anticipation
clinical features of myotonic dystrophy
Mild –> classic –> congenital
affects skeletal, eyes, endocrine and CNS
What is the affected gene and normal action of this gene for Retinoblastoma?
what is the common mutation?
RB1 = tumour suppressor gene ( regulates G1 –> S phase)
loss-of-function mutation= uncontrolled cell division
2-hit hypothesis inheritance
Clinical feature of Retinoblastoma
leukocoria (white pupils, clearer in photos)
What is the affected gene and normal action of this gene for Neurofibromatosis?
what is the common mutation?
NF1 and NF2 gene
= partial/complete loss of function
Clinical features of NF1 and NF2
NF1
-changes in pigmentation
-growth of tumpurs along nerves in skin/brain
NG2
-growth of noncancerous tumours on nervous system
-hearing loss and deafness
-vestibular schwanomas
What is the affected gene and
what is the common mutation of colour blidness?
OPN1LW (yellow/orange)
OPN1MW (yellow/green)
caused by unequal crossing over
What is the affected gene and normal action of this gene for Hypophosphate Rickets ?
PHEX gene = coordinates bone mineralisation and systemic phosphate homeostasis via directly regulating mineralising and producing FGFR3
What is the affected gene and normal action of this gene for DM dystrophy?
what is the common mutation?
DMD gene = produces dystrophin - critical structural protein
Clinical features of Hypophosphate Rickets
Weakened bones
curavture of spine
bowing of legs
Clinical features of DM Dystrophy and treatment
skeletal and cardiac muscle affected
growers manoeuvre
exon skipping and reading through STOP codon
What is the affected gene and normal action of this gene for Haemophilia?
F8 gene = A = clotting factor VIII
F9 gene = B = clotting factor IX
What is the affected gene and normal action of this gene for kennedy’s Disease?
what is the common mutation?
AR Gene
CAG reaptes > 35 in AR protein
toxic gain-of-function
-protein aggregates are toxic to motor neurons = spinal and bulbar muscle atrophy
Clinical features of Kennedy’s disease
progressive muscular atrophy disorder of motor neurons in the spinal cord
- protein aggregates are toxic to motor neurons → spinal and bulbar muscle atrophy
in males:
infertility and gynecomastia
Clinical features of haemophilia
Excessive bleeding: (most common symptom) - can occur after injuries, surgeries, or dental procedures.
Spontaneous bleeding: without any apparent injury.
Joint bleeding: Bleeding into the joints, particularly the knees, ankles, and elbows,
Muscle bleeding:
What is the affected gene and normal action of this gene for leigh’s Disease?
MTATP6 = encodes ATP syntahse 6
deficicnces in ATP production and oxidattive phospphorylation
