Genetics Flashcards
Autosomal Recessive
◙ If Both Parents are carriers
• 25% chance of a child to be affected
50% chance of a child to be carrier
If one parent is affected and other carrier
→ 50% chance of a child to b affected
. ~~And 50% chance of
parent does NOT have the
a child to be a Carrier
Autosomal Recessive Autosomal Dominant X-Linked Recessive
Autosomal Recessive Autosomal Dominant X-Linked Recessive
AR conditions
Sickle Cell Anemia
Thalassemia
Haemochromatosis
Cystic Fibrosis
Congenital Adrenal hyperplasia
( 21-hydroxylase
Deficiency).
Autosomal Dominant
If One parent is Affected
—50% chance of a child to be affected
→ 25% chance of grandchild to be affected.
Note: there is no carrier state of AD condition
If parent does NOT have the
gene → 0% he will pass to
his/her child.
AD conditions
Huntington’s Disease
Neurofibromatosis
Autosomal Dominant polycystic kidney disease ADPKD
BRCA gene (breast cancer)
VWD
Hereditary spherocytosis
Multiple Endocrine
Neoplasia (MEN)
X linked recessive
If Mother is Carrier,
→ 50% chance of a Male child to be affected.
◙ If Father is affected,
→ 0% chance of a Male child to be affected
100% chance of a Female child to be carrier.
X linked recessive conditions
G6PD deficiency
Haemophilia
Duchenne Muscular
Dystrophy (DMD
37-year-old man is concerned about the genetic risks for his children. He
explains that his paternal grandmother had medullary thyroid carcinoma and
passed away in his fifties.
Additionally, his father has recently been diagnosed
with hyperparathyroidism, and his paternal uncle has had a pheochromocytoma.
He is worried about inheriting this genetic condition and the possibility of
passing it on to his children. What is the most likely inheritance pattern of this
condition?
Correct answer → A) Autosomal dominant.
This family history is suggestive of Multiple Endocrine Neoplasia type 2 (MEN 2),
an autosomal dominant condition.
MEN 2 is characterised by the presence of
medullary thyroid carcinoma, hyperparathyroidism, and pheochromocytoma,
as described in the family.
The autosomal dominant inheritance pattern means
that each child of an affected parent has a 50% chance of inheriting the
condition.
Scenario:
A 36-year-old woman, gravida 3 para 2, at 18 weeks gestation is concerned
about chromosomal abnormalities due to a family history of Edwards
syndrome (Trisomy 18). She has not undergone any prenatal screening tests.
Question: What is the most appropriate investigation to confirm the presence
of Edwards syndrome?
Chorionic villus sampling (CVS) (performed between 11-14 weeks) is less
suitable at 18 weeks.
• Amniocentesis (performed between 15-20 weeks) is the most appropriate
diagnostic test at this stage, providing a definitive analysis of fetal
chromosomes.
• Doppler ultrasound of the umbilical artery and Foetal echocardiography
are not diagnostic for chromosomal abnormalities.
• Detailed ultrasound at 20 weeks can identify physical abnormalities but
does not confirm chromosomal conditions.
Remember, For Fetal Karyotyping:
◙ Before pregnancy → Preimplantation Genetic Diagnosis (PGD).
◙ 11-14 Week gestation → Chorionic Villous Sampling.
◙ 15-20 Week gestation → Amniocentesis.
A 29-year-old woman who is 8 weeks pregnant attends the antenatal clinic
for the first time with her husband who has sickle cell anemia.
She is
unaware of her sickle cell status. She is from West Africa.
What is the most
appropriate initial investigation to assess the risk of their unborn child
inheriting sickle cell anemia?
→ Maternal haemoglobinopathy screening.
• Since the father has sickle cell anemia (known).
And the mother’s status of the disease is unknow (and she is African) ↑ risk.
→ Assessing the mother’s carrier status of sickle cell disease is crucial.
• Maternal haemoglobinopathy screening will determine:
√ If she is a carrier of sickle cell trait → significant risk for the child to inherit
sickle cell disease.
√ If she is not a carrier → the child “may” inherit the sickle cell trait, but will
not develop the disease
Knowing that the father, sister, and brother had experienced episodes of
malignant hyperthermia following general anaesthesia. The following
pedigree shows the malignant hyperthermia among the family. What is the
mode of inheritance?
√ This pedigree shows → Autosomal dominant pattern.
√ Note that in each generation, there is at least 50% affected people.
√ Also, be aware that malignant hyperthermia is an autosomal dominant
condition.
◙ Examples of Autosomal Dominant Conditions:?
Huntington’s Disease, Neurofibromatosis,
Autosomal Dominant Polycystic
Kidney Disease (ADPKD),
BRCA gene (breast cancer),
VWD,
Hereditary
spherocytosis.
Q) A 72-year-old man has Huntington’s disease. What is the likelihood that
her grandchild will develop Huntington’s disease?
Answer → 25%.
Remember: Regrading Autosomal Dominant Conditions:
◙ If One parent is Affected
→ 50% chance of a child to be affected.
→ 25% chance of a Grandchild to be affected.
◙ Note: there is no carrier state of autosomal dominant conditions. If a parent
does NOT have the gene → 0% he will pass to his/her child.
Q) A 72-year-old man has Huntington’s disease. What is the likelihood that
her child will develop Huntington’s disease?
Answer → 50%.
Q) A 72-year-old man has Huntington’s disease. His daughter tested negative
for Huntington’s disease gene (ie, she does not have the gene). What is the
likelihood that her child will develop Huntington’s disease?
Answer → 0%.
• Huntington’s disease is autosomal dominant with complete penetrance.
• There is no carrier state of this disease.
• It is either they have the gene (50% that they will pass it to their child) or
they do not have the gene (0% they will pass it).
An 8-year-old boy has recently been diagnosed with celiac disease and type 1
diabetes mellitus. What is the most likely associated gene?
→ HLA-DQ2 gene.
(DQ: Drama Queen ▐ 2, for 2 diseases (DM, Celiac).
What is the strongest genetic risk factor for Alzheimer’s disease (AD)?
Apolipoprotein E gene (APOE e4 allele)
→ APOE ε4
A 46-year-old man has recently been diagnosed with invasive breast cancer.
His father has a history of prostate cancer, and his 2 sisters have breast
cancer. What is the most likely gene affected?
→ BRCA 2 gene.
• HLA-DQ2 → Celiac disease + Type 1 Diabetes mellitus.
• HLA-DQ3 → Type 1 Diabetes mellitus.
• HLA-DQ8 → Celiac disease, Rheumatoid arthritis, and Juvenile diabetes.
HLA B 27
I ate (8) too (2) much gluten at Dairy Queen
→ HLA-DQ8 and HLA-DQ2 linked to Celiac disease (gluten).
• HLA-B27 →
Ankylosing spondylitis, Psoriatic arthritis,
Reactive arthritis,
Inflammatory bowel disease.
• BRCA (1 or 2) → Breast cancer.
• BRCA 2 → Breast cancer in woman + Prostate/ Breast cancer in men.
• APOE ε4 gene = Apolipoprotein E gene (APOE e4 allele) → Alzheimer’s.
If a Family has Widespread Breast Cancer:
• Think → BRCA gene mutation (either BRCA 1 or BRCA 2 mutation, both can
cause breast cancer).
• BRCA genes are inherited as autosomal dominant.
• Important:
In addition to breast cancer in women, if men are also involved with breast
and or prostate cancer → BRCA 2 mutation is more likely than BRCA 1.
Hereditary Haemochromatosis.
♦ Autosomal Recessive.
♦ ↑intestinal Absorption of Iron → Iron Accumulation “Deposition” in
Tissues, such as:
• Liver “
The main organ of iron deposition” → Hepatomegaly, Cirrhosis →
HCC = Hepatoma “Hepatic Cancer”
.
• Pancreas → Diabetes Mellitus.
• Skin → Bronze Skin (Hyperpigmentation).
• Joints → Arthropathy.
• Heart → Arrhythmia,
Cardiomyopathy →
Dyspnea.
Triad in heamochromatosis
Remember in Haemochromatosis:
→ the Haemochromatosis (Due to Cirrhosis and iron deposition).
TRIAD: Hepatomegaly + DM + Bronze Skin ▐ ± Arthropathy.
♠ Remember that the “Liver” is the most likely organ to get cancer in
Haemochromatosis
Due to Cirrhosis and iron deposition).
