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Genetics- lecture 9- Disease

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winniesmith1's version from 2017-05-15 13:49

Section 1

Question Answer
What is the normal composition of RBCsMulti-subunit Iron containing protein (tetramer): -2 alpha and 2 beta subunits -Heme group -Molecular Wt. 64500 Daltons
In RBCs how are the heme groups distributed one per subunit. has an iron atom. carries 02.
what is normal adult Hb HBA or HBA1 (98%)
How many genes code for Hb6 (multigene system)
What are the 6 different polypeptides in Hb Alpha(141 aa) Beta (146aa) Gamma (146aa) Delta (146aa) Epsilon (141aa) Zeta (141aa)
What type of Hb genes are most prevalent during gestational age alpha highest (50%), gamma high (40% but declines near end) B increases towards birth. Zelta declines over first 8 weeks.
What type of Hb genes are most prevalent after birth (postnatal age)Alpha still highest (50%) Beta second highest rises to 45%. gamma declines from 25 to 5%. Small amounts of delta present 5%.
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Section 2

Question Answer
What are the embryonic Haemoglobin's present at 7-10 weeks of gestation Gower I, Gower II, Portland
What are foetal haemoglobin's HB F (alpha2gamma2). 85% of HB in new born, declines rapidly after birth (10-15 % after 4 months)
What makes up adult Hb HB A or HBA1 (alpha 2 beta 2). 98% of total HB, rest is HB A2 (alpha 2 delta 2)
how do you identify HB variation by electrophoresis
how does electrophoresis workIt works on the basis of physical or chemical properties such as: (1) size , (2) shape (3) electrical charge -Gels can be made from various chemicals (e.g. agarose) -Samples loaded, voltage applied -Negatively charged Samples migrates toward “+” electrode -Smaller DNA/Protein fragments migrate faster
Describe mutations in Hb300 Variants, >90% AA substitutions, 60% in Beta Chain genes.
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Section 3

Question Answer
What is the cause of sickle cell anaemiaGlutamate (glu), a negatively charged amino acid, is replaced by valine (val), which has no charge. (Autosomal recessive)
Describe sickle cell anaemiaRBCs are sickle shaped (caused by abnormal Hb crystallising), so cause anaemia. Results from defective Hb, causing Hb to stick together and RBCs to be damaged.
What are the symptoms of sickle cell anaemia Complications from low oxygen supply to tissues: Pain, organ damage, strokes, increased infections, etc. (pg 11)
Where is sickle cell most common?-Incidence highest among Africans and Indians. -Common in Malarial Regions: Heterozygotes protected from Malaria, Heterozygote advantage.
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Section 4

Question Answer
What does Thalassemia or Cooley's anemia cause Quantitative defects: amounts of Hb reduced. Decreased chain production, mainly of alpha and beta.
Describe alpha thalassemia minor-alpha/ alpha thal -no anemia -3 - 10% Hb Barts at birth - usually normal adult with may be a trace of Hb H
Describe alpha thalassemia majorHbH disease, Hydrops Fetalis. -More than two genes deletions
What is alpha thalaseemiadecreased alpha chains
What is beta thalaseemiasdecreased synthesis of beta-globin chains
Describe beta thalassemiaexcess of alpha-globin chains--> homotetramers. -aggregate to form insoluble inclusions in erythroid precursors  highly toxic. -MUTATIONS! MANY (Replication, Transcription, Insertion, Deletion, Reading frame Errors). -If Any thing can go wrong, it will!. - Autosomal Recessive .
Describe thalassemia major No production of beta globin -> No HBA, severe anemia and iron overload, chronic transfusion dependent, bones thin, skull distorted (Tower skull), short life span
Describe thalassemia minorCarry one normal beta globin gene, abnormal erythrocytes, little or no anemia
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Section 5

Question Answer
When does a metabolic disorder occur when the body is Not able to metabolize foods/Drugs in the usual way. multiple enzymes needed, if mutation occurs and enzyme does not form then there is a block in system
Describe PKU or phenylketonuria-Autosomal recessive disease. -Defective allele does not synthesize enzyme that controls use of phenylalanine. -Without enzyme, Phenylalanine converted to poisonous substance. -If untreated, reduced brain size, poor motor coordination, mental retardation.
What are the medical applications of genetics1)Genetic Counselling- What is GC and what it involves 2)Genetic Screening- Why is it needed and how it can be used.
What is genetic counselling?Communication process- address individual concerns relating to development / transmission of hereditary disorder. Includes; Strong communicative and supportive element so that those who seek information are able to reach their own fully informed decisions without undue pressure or stress
What is a consultandindividual who seeks genetic counselling.
What are the steps in genetic counselling1) Diagnosis - based on Family history (pedigree), medical examination and Lab investigations. 2) Risk assessment and Calculations; -Simple: based on patterns of inheritance (AD, AR, X-linked) -Bayes: Prior, Conditional and Posterior 3) Communication of results and Discussion of Options 4) Long-term contact and support
What are genetic counselling risk calculations and what should be taken into consideration-straightforward counselling situations - knowledge about Mendelian inheritance (ratios) is primarily needed. -Problems: delayed age of onset, reduced penetrance. -as rule of thumb: recurrence risks should be quantified, qualified and placed in context.
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Section 6

Question Answer
What is bayes theorm; probability theorem, alternative hypothesis- based on Prior probability, conditional probability, joint probability---> to give posterior probability (likelihood of disease ))
how do you work out a carrier risk calculationusing (p+q)^2= p^2 + 2pq +q^2
What is the goal of genetic screeningearly recognition of a disorder
Why is genetic screening doneto prevent or reverse the disease process. to allow reproductive decisions.
What tests are used (price)inexpensive tests. -Good Detection- Accurate and correct. -Carrier detection tests & definitive tests.
What are the types of genetic screening -Prenatal Diagnosis (Amniocentesis, Chorionic villus sampling (CVS), Ultrasonography). -New-born Screening: PKU, Galactosemia, CF, HB,SCA, Thalassemias. -Heterozygote screening; Tay-Sachs: Jewish population, SCA (African), CF (White European), Thalassemia (Mediterranean, Southeast Asia). -Pre-symptomatic screening (HD, Cancers).
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Section 7

Question Answer
Carrier freq. of sickle cell in African pop.1 in 10
Carrier freq. of gaucher disease in ashkenazi jewish1 in 15
Carrier freq. of alpha-thalassemia and beta-thalassemia in Asian pop.1 in 20 and 1 in 50
Carrier freq. of cystic fibrosis in European pop.1 in 25-29
Carrier freq. of Beta-Thalassemia, Cystic Fibrosis and Sickle Cell in the mediterranean pop.1 in 25, 1 in 29 and 1 in 40
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