Genetics Flashcards

Question

Cystic fibrosis

Answer 1

Autosomal recessive Exocrine secretion, increased chloride in sweat 1:2000, 1:25 caucasian carriers CFTR gene - on ch7, usually F508del (produces chloride ion protein responsible for anion transport) Excess mucus production blocking ducts of mucus secreting organs - recurrent chest infections, infertility, pancreatitis, cirrhosis, intestinal obstruction, osteoporosis, diabetes + congenital absence of vas deferens in males 98% infertility

Answer 2

Autosomal recessive HbSS homozygous or HbAS heterozygous Point mutation on beta globulin chain of Hb Single base change GAG to GTG, so hydrophobic protein made instead of hydrophilic Loss of RBCs due to loss of elasticity and sickling, short life span 10-20 days, haemolysis in spleen Blood film shows sickling, + Howell-Jolly bodies Vaso-occlusive crisis Acute chest syndrome - fever, chest pain, SOB, pulmonary infiltrates on XR Aplastic crisis - parvoB19 trigger Splenic sequestration crisis Haemolytic crisis - esp if G6PD also Treat - cyanate, hydroxyurea, analgesia, penicillin, vaccinations, blood transfusion, BM transplant

Answer 3

Reduced rate in synthesis of 1 of globulin chains making Hb More in mediterranean/Arab/Maldives Anaemia due to hypochromia (low intracellular Hb), excess unimpaired chain See microcytosis, target cells, hypochromia

Answer 4

There are 4 alpha globin chains 1 affected - silent carrier 2 affected - trait - mild hypochromic anaemia 3 affected - haemoglobin H disease, moderate anaemia with splenomegaly 4 affected - Bart's hydrops - in utero death See tissue hypoxia, hydrops fetalis In fetus start seeing distree after 12 weeks when Hb Portland is replaced by Hb Barts (higher affinity to oxygen so inhibit delivery to tissues)

Answer 5

1:10,000 in UK, 1:7 in Cyprus Major - homozygous Minor/trait or intermedia - heterozygous Fatigue, anaemia, jaundice, SOB, skeletal abnormalities, hepatosplenomegaly, haemochromotosis Usually present at 6months, when fetal Hb to adult Hb Treat for major - blood transfusions, folic acid, vitD and calcium, chelation therapy, splenectomy, BM transplant

Answer 6

METACENTRIC - have the centromere in the middle (1, 3, 16, 19, 20) ACROCENTRIC - have the centromere close to one end (13, 14, 15, 21, 22) -these are the chromosomes usually involved in balanced translocations SUB-METACENTRIC - have centromere in-between Chromosomes have a short (p = petit) and a long (q) arm??

Answer 7

Basic nuclear protein around which the DNA molecule is tightly bound - makes up about 50% of the mass of a chromosome (1:1 histone:DNA) - rich in lysine or arginine (~25%, basic amino acids) - the genes coding for histone protein are clustered and tandemly repeated 30-40 times in humans

Answer 8

Western blotting - used to detect protein Northern blotting - used to detect RNA Southern blotting - used to detect specific DNA sequences PCR used to amplify DNA sequences

Answer 9

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY X-linked recessive (so males!) - deficiency of erythrocyte glucose-6-phosphate dehydrogenase. Enzyme plays key role in Pentose phosphate pathway, catalysing conversion of glucose-6-phosphate to 6-phospho-gluconolactone - may be asymptomatic, or neonatal jaundice, chronic haemolytic anaemia, haemolysis induced by eating fava beans, sulphonamides, primaquine and infection - female carriers may suffer haemolytic crises

Answer 10

- autosomal dominant - unstable length mutation in the number of CTG repeats - correlation between the length of the repeats and severity of the disease - the length of the repeat may change during transmission, altering the severity of the disease from one generation to the next - no neonatal disease if the father has the disease. With maternal disease, there is a 20% risk of neonatal death or severe neonatal hypotonia and mental handicap - clinical features include frontal balding, distal muscle and sterno-mastoid weakness, gonadal atrophy in males, difficulty relaxing a clenched fist, cardiac conduction defects and retinopathy - pre-natal diagnosis by direct DNA analysis

Answer 11

- autosomal recessive - deficiency of phenylalanine hydroxylase - if early low phenylalanine diet, associated with normal life span although some degree of learning disability may be present - after childhood (6-8years), the brain is less susceptible to the harmful effects of high phenylalanine levels - need to return to low phenylalanine diet in pregnancy, or risk of fetal structural abnormalities including microcephaly - causes high blood and urine phenylalanine levels - neonatal screening using the Guthrie test

Answer 12

Duchenne - X-linked recessive - null mutation resulting in absence of dystrophin on muscle biopsy - onset in childhood (by age of 5) with proximal muscle weakness, calf pseudo-hypertrophy; mild learning disability in 25%, majority wheelchair bound by age 12 with death in 20s. Becker - X-linked recessive - reduced dystrophin on muscle biopsy - onset in late childhood, calf pseudo-hypertrophy. Wheelchair bound by age 25, life-span may be normal - better prognosis than Duchenne Pre-natal diagnosis for Duchenne / Becker muscular dystrophy by direct DNA analysis (CVS / Amnio)

Answer 13

- autosomal recessive - disorder of the metabolism of methionine due to a deficiency of cystathionine beta synthase or methionine synthase - can also be caused by a deficiency of vitamins B6, B12, or folate -> multi-systemic disorder of the connective tissue, muscles, the CNS and CVS - accumulation of the amino acid homocysteine in the serum and increased excretion of homocysteine in the urine Flushed cheeks Tall, thin build resembling Marfanoid habitus Long limbs Pes cavus Genu valgum Pectus excavatum and Pectus carinatum Intellectual disability Seizures Psychiatric disease Eye abnormalities Vascular disease

Answer 14

A - factor VIII deficiency B - factor IX deficiency - both are X-linked recessive and clinically indistinguishable - spontaneous bleeding into joints / soft tissue or following trauma - treated by factor VIII or IX replacement - male fetus inherits Y chromosome from father and therefore cannot be affected if the father has the disease. 50% risk of male fetus being affected if the mother is a carrier (inherits one of 2 X chromosomes).

Answer 15

X-linked recessive - mutation in androgen receptor gene - female phenotype, normal breast development, absent uterus with blind-ending vagina; paucity of pubic and axillary hair - testes found in abdomen or inguinal canal - increased risk of gonadoblastoma * - infertility - karyotype 46XY

Answer 16

- genetic defect in collagen metabolism Type I - autosomal dominant, associated with recurrent fractures, blue sclera, otosclerosis leading to conduction deafness. Normal life span Type II - variable inheritance with a 3% recurrence risk - causes perinatal death with multiple fractures at birth

Answer 17

- autosomal recessive - carrier frequency 3% in Caucasians - Z-allele is a point mutation which interferes with the release of anti-trypsin from hepatocytes - diagnosis by protease inhibitor activity assay or DNA analysis (CVS or amnio) - associated with juvenile cirrhosis, emphysema

Answer 18

- Autosomal dominant - 50% risk of offspring inheriting the condition + 25% caused by new mutation - associated with lens subluxation, aortic aneurysm, arachnodactyly, long limbs and joint laxity - average life-span 40-50 years

Answer 19

- mostly autosomal dominant although some variants may be autosomal recessive - defect in von Willebrand factor (vWF), which promotes platelet adhesion to sub-endothelium and binds and stabilises factor VIII - factor VIII activity may be reduced -> prolonged bleeding time and reduced platelet aggregation with ristocetin - infection, stress, inflammation, physical exercise and recent surgery and pregnancy cause raised vWF and factor VIII levels

Answer 20

- used as a screening test to identify variant and abnormal haemoglobins, including HbA1, HbA2, HbF, HbC, HbS Should be: HbA 1: 95%-98% HbA 2: 1.5%-3.5% HbF: < 2% (age-dependent) HbC: Absent HbS: Absent

Answer 21

In liver, urea then excreted by kidneys Rate limiting step controlled by enzyme carbamoyl phosphate synthetase I One turn of the urea cycle: - consumes 2 molecules of ammonia - consumes 1 molecule of carbon dioxide - creates 1 molecule of urea ((NH2)2CO - regenerates a molecule of ornithine for another turn

Answer 22

Neoplasms - Retinoblastoma - autosomal dominant, often bilateral. Increased susceptibility to second tumours especially osteosarcoma. Locus 13q14 - Familial poliposis coli - autosomal dominant. May be associated with osteomas, lipomas and fibromas (Gardner’s syndrome) - Multiple endocrine neoplasia type I - autosomal dominant, adenomas of the pituitary, parathyroid and islet cell - Multiple endocrine neoplasia type II - autosomal dominant, medullary carcinoma of the thyroid, phaeochromocytoma and parathyroid tumour Pre-neoplastic conditions - Neurofibromatosis - autosomal dominant, gliomas of the brain and optic nerve, acoustic neuromas, meningioma, phaeochromocytoma - Tuberous sclerosis - autosomal dominant, glial tumours, harmatomas - Xeroderma pigmentosa -autosomal recessive, basal and squamous cell carcinoma of the skin, malignant melanoma - Fanconi’s anaemia - autosomal recessive, acute leukaemias - Ataxia telangiectasia - autosomal recessive, acute leukaemia, lymphoma and breast cancer in females