x-linked pattern Flashcards
What is the manifestation of Duchenne Muscular Dystrophy?
Enlarged calves and wasting of the thigh muscle
For men, tends to be lethal before age of 30
Duchenne muscular dystrophy has high or low reproductive fitness
Low
Difference between Duchenne and Becker muscular dystrophy
Less severe mutation in DMD leads to Becker
More severe mutation in DMD leads to Duchenne
When a child is affected, look for the disorder in maternal relatives. Which mode of transmission is this?
X-linked recessive
What is manefestation of hemophilia A
inherent deficiency of clotting factor 8, resulting in increased tendency to bleed
Relationship between hemophilia A and allelic heterogeneity
Inversion of intron lead to incorrect splicing
while other mutation leads to hemophilia A
How is Duchenne muscular dystrophy transmitted?
X-linked recessive
How is Hemophilia A transmitted?
X-linked recessive
What causes X-linked SCID and what is the manifestation?
Due to defect in SCIDX1 gene, it leads to defect in gamma chain of receptor for several interleukins(IL2RG), which result into immature T-cell. This results in a deficiency of normal B-cell function.
What happens if a woman who is carrier of Duchenne have a symptoms? How can it be explained?
It is due to skewed X-inactivation. The number of cells that contain the active X chromosome with the mutation in DMD are larger than cells that contain the active X with functional DMD gene.
How is red/green color deficiency transmitted?
X-linked recessive
How is Rett syndrome transmitted?
X-linked dominant
What mostly happens to males who have X-linked dominant disorder?
Die in utero
What is Rett syndrome?
Genetic brain disorder
Manifestation of incontinentia pigmenti
rashes and blisters in early life and later, patches of hyperpigmentation
How is incontinentia pigmenti trasmitted?
X-linked dominant
Transmission of vitamin D resistant Rickets
X-linked dominant
How can it be explained if a person who have inherited the mutant allele of autosomal dominant disorder does not display the disease phenotype?
A disorder is non-penetrance
What incomplete penetrance?
Penetrance may be dependent on age, (adult onset disease),
How do we calculate recurrence risk based on penetrance of 80% for autosomal dominant disease?
recurrence risk normal is 50%, so 50*80 / 100 = 40%.
So recurrence risk is 40% when penetrance is 80%
What does variable expression mean?
severity of genetic disease is different due to some factors
What are 3 factors affecting variable expression
- Random chance
- Other genetic factors or sex influence
- Environmental exposure
How is variable expression related to Hemochromatosis?
It is more severe in male , and premenapausal females will menstruate and lose iron.
What is hemochromatosis and mode of transmission?
an iron overload disorder (autosomal recessive)
What is xeroderma pigmentosum and mode of transmission?
Decreased ability to repair DNA damage caused by UV rays (autosomal recessive)
Explain Neurofibromatosis type I in terms of penetrance and variable expression
All patients with the mutant NF1 gene express at least some signs of the disorder (High penetrance), but severity is different (variable expression)
What is pleiotropy
A disease causing mutation affects more than one organ system
What is pleiotropy
A disease causing mutation affects more than one organ system
What is cause and manifestation of marfan syndrome?
due to mutation in fibrillin-1 gene, skeletal abnormalities (long limb), hypermobile joints, ocular abnormalities, cardiovascular disease
How is marfan syndrome transmitted?
Autosomal dominant
cause and manifestation of osteogenesis imperfecta
brittle bones, blue sclera due to mutation in gene encoding pro-collagen
Example of disease that shows pleiotropy
Marfan syndrome, osteogenesis imperfecta
What is locus heterogeneity?
Mutation at different loci or gene cause same disease phenotype.
Example of disease that show locus heterogeneity
Osteogenesis imperfecta (mutation in chromosome 7 and 17 shows defect in collagen Breast cancer (mutation in BRCA1 &2, cause increased predisposition to breast cancer)
Example of autosomal recessive inheritance + locus heterogeneity
Congenital deafness
pathology of CF
Lung : mucus in lung is very viscous and is not cleared from lung or airway causing recurrent infection and inflammation leading to tissue damage.
Pancrea : pancreatic duct gets clogged because of viscous mucus, leading pancreatic insufficiency and auto degradation
