Genetics Flashcards
What is Autosomal Dominant Inheritance?
- Heterozygous for the dominant allele;
- On each pregnancy an affected individual has 50% chance of passing it;
- Homozygous (2 copies of the dominant allele) is rare.
Give examples of Autosomal Dominant Inheritance?
- Huntington’s disease
- Polycystic kidney disease
- Neurofibromatosis
What is Autossomal recessive inheritance?
- Both parents MUST be carriers (only one copy) or have the disease themselves (two copies);
- The trait (disorder) can only manifest when 2 copies of the gene (one from each parent) are inherited.
Give example Autossomal recessive inheritance conditions?
- Cystic fibrosis
- Sickle cell anaemia
- Thalassemia
- Congenital adrenal hyperplasia
- Haemochromatosis
- Wilson’s disease
CATCH WILSON
Cystic fibrosis
Anaemia (sickle cell)
Thalassemia
Congenital adrenal hyperplasia
Haemochromatosis
Wilson’s
Autosomal recessive with both parents being carriers (they don’t have the disease). What are the chances of an affected child?
Ex: cystic fibrosis
- 25% chance of an affected child
- 50% chance of a child being a carrier
- 25% chance of a child who doesn’t have the disease and is not a carrier.
What is X-linked recessive inheritance?
- Disorders that are caused by mutations in genes on the X chromosome;
- Males only have a single X chromosome and if affected that is all that is needed to cause the disease;
- Females require 2 copies of X chromosome to fully express the disease (since it’s recessive);
- On a female if only one X affected is passed, she becomes a carrier
Examples of X-linked recessive inheritance? Sim
- Haemophilia A
- Duchenne muscular dystrophy
- G6PD deficiency
What are the chances of having an affected child in X-linked recessive inheritance?
- Father doesn’t have the disease;
- Mother is a carrier.
- There is a 25% chance of having a boy affected
- 25% chance of having a female carrier.
A couple is expecting a boy. The mother is a carrier for haemophilia A. The father doesn’t have the disease.
- What are the chances of an affected child?
X-linked recessive inheritance
- 50 %
- Because it already says it’s a boy.
- There is 50% chance of having a healthy boy and 50% chance of an affected child.
A couple is expecting a baby. The father has haemophilia A. The mother is normal.
- What are the chances of an affected child?
X linked recessive inheritance
- There is 0% chance of an affected child.
- 50% chance of the child being a carrier
- All females will be carriers
- All boys will be unaffected and won’t be carriers.
Example of X linked dominant inheritance.
- Fragile X syndrome.
A 25 yo woman just gave birth. Her father (the grandparent) has Huntington’s disease. She hasn’t been tested and doesn’t present any symptoms.
- What are the chances of the baby being affected?
- Huntington’s is autosomal dominant.
- The woman has a 50% chance of being affected.
- Her baby has half her chances so 25% chance of being affected.
- If you knew for sure that the mother of the baby was affected, than the baby would have had 50% chance of being affected. Since it’s not known the status of the mom (she could be affected or not have the gene) than the baby has 25% chances.
Describe the autosomal dominant pedigree chart.
- Every affected person has at least one affected parent.
- Both males and females can be equally affected.
- Trait does not skip generations.
- Approximately half of the offspring of an affected person, are affected.
- Unaffected individual do not pass the trait.
Describe the autosomal recessive pedigree chart.
- Affected individuals often have unaffected parents (parents will be carriers only);
- It can skip generations;
- Approximately 25% of offspring are affected when both parents are carriers;
- All children of two affected parents are affected;
Describe the X-linked recessive pedigree chart.
- More males are affected than females;
- No male to male transmission (dad’s can only give Y chromosome to their sons);
- Affected males often have unaffected parents (happens when the mother is the carrier).
- All daughters of affected males are carriers (males can only pass the affected X chromosome);
- Half the sons of carrier females are affected.
Describe the X-linked dominant pedigree chart.
- Both males and females can be affected;
- No male-to-male transmission;
- Affected fathers will have all affected daughters;
- Traits do not skip generations.
A child has cystic fibrosis.
What are the chances of the grandfather (paternal) being a carrier?
- Cystic fibrosis is autosomal recessive.
- For the child to be affected both parents HAVE to be carriers. Hence it is confirmed that the dad is a carrier since the child is affected.
- The grandfather has a 50% chance.
What will be the chances of inheritance of sickle cell anaemia if:
- One parent is homozygous (for sickle);
- The other parent is heterozygous (for sickle).
- 50% chances of offspring being affected;
- 50% chances of offspring being carriers.
What are the investigations done in Duchenne muscular dystrophy?
Initial test: creatinine kinase
Others
- Muscle biopsy
- Genetic testing (after +ve biopsy)
DDx between:
- Duchenne muscular dystrophy
- Becker muscular dystrophy
- Both x-linked recessive
Duchenne
- Onset of symptoms by age 3
- Diagnosis between 4-8 years.
Becker
- Later onset of symptoms (16 years)
What are the congenital defects associated with Down syndrome?
- Atrioventricular septal defect
- Duodenal atresia
What are the symptoms of DiGeorge Syndrome?
CATCH-22
-
Cardiac abnormalities -
Abnormal face -
Thymic aplasia (absent) -
Cleft palate -
Hypocalcaemia/Hypoparathroidism - Chromosome
22abnormalities
What are the symptoms of Angelman syndrome?
Neonatal period:
- Normal head circumference;
- Developmental delay signs by 6 months;
Childhood period:
- Severe developmental delay;
- Disproportionate head circumference growth.
What are the features of Klinefelter syndrome?
AKA: 47 XXY
- Affects males only
G-FELTER
- Gynecomastia
- Facial hair (low)
- Estrogen is ⬆︎ and testoterone is ⬇︎
- Long limbs
- Tall and slim
- Elevates FSH and LH
- Rage (agressive behaviour)
Hypogonadism
- Small testes
- Azoospermia (no sperms in semen)
- Infertility
How is the diagnosis of Klinefelter syndrome done?
Karotyping - chromossome analysis 47 XXY.
What are the symptoms of Huntington’s disease?
Autossomal dominant / Family Hx- Changes of personalities
- Self neglect, clumsiness
Memory loss- Poor concentration
Chorea (jerky involuntary movements)- Dystonia
- Rigidity
- Dementia
➜ Symptoms in next generation appear earlier and earlier.
Describe how investigation for potential genetic diseases is done?
Before pregnancy:
- Preimplantation genetic diagnosis (in vitro)
After pregnancy:➜ Week 11-14 (late 1st trimester)
- Chorionic villus sampling (placenta testing)
➜ Week 15-18 (early 2nd trimester)
- Amniocentesis (amniotic fluid tested)
What is the prenatal test done in sickle cell anaemia?
1st line:Maternal haemonoglobinapathy
- To test if the mother carries the sickle cell trait.
- If the test is positive than CVS or amniocentecis can be done.
What is the mode of inheritance for BRCA1 gene mutation?
Autosomal dominant with incomplete penetrance.
What is the gene mutation associated with MEN breast cancer and prostate cancer?
BRCA2.
What are the features of Alport syndrome?
- X-linked disease
- Haematuria + Proteinuria
- End stage renal disease
- Sensorineural hearing loss
- Eyes abnormalities
What is the gene associated with Diabetes and coeliac disease?
HLA-DQ2.
