Heredity

Question 1

Two autosomal dominant disorders

Answer 1

Huntington’s Disease

Achondroplastia

Question 2

Three autosomal recessive disorders

Answer 2

CF
Albinism
Tay-Sachs

Question 3

One more time: what phase can we karyotype in?

Answer 3

METAPHASE.

Question 4

What specific kinds of Down’s congenital heart problems occur?

Answer 4

Tetralogy of Fallot

Question 5

Klinefelter’s Syndrome : what’s the karyotype?

Answer 5

44 + XXY

More Xs = more problems (intellectual varying degrees)

Question 6

Turner’s Syndrome: what’s the karyotype?

Answer 6

44 + X + nil (only 45 chromosomes in total)

Question 7

Turner syndrome - symptoms?

Answer 7

Short, webbed neck, sterile (no ovaries), limited intellectual disability.
Risk of cancer with Y mosaicism .
Aorta coarctation

Question 8

Disease with an abnormality of chromosome structure.

(Also what’s the abnormality?

Answer 8

Cri du chat

slightly shortened chromosome 5

Question 9

Translocation named after an american state. What chromosomes, what result?

Answer 9

Philadelphia translocation; 9 and 22; leukaemia.

Question 10

Other translocation, results in BURKITT’S LYMPHOMA. What chromosomes, what gene becomes dyregulated and constitutively expressed?

Answer 10

8/14; myc gene.

Question 11

Reinsertion. Associated with what place, with what disease?

Answer 11

Hiroshima survivors; leukaemia

Question 12

What disease is listed as two point mutation diseases?

Answer 12

Sickle Cell Anaemia

They also point out oncogenes.

Question 13

Four types of mutation risks in the lecture.

Answer 13

1. ionising radiation
2. non-ionising (UV)
3. drugs/Chemicals (chemotherapy, asbestos)
   esp alkylating drugs
4. viruses (inserted genes e.g retroviruses)

Question 14

What drugs are especially mutagenic?

Answer 14

Alkylating drugs e.g. methotrexate for arthritis.

Question 15

Two diseases for GENE IMPRINTING and which parent do they come from? What chromosome is DELETED?

Answer 15

Prader-Willi Syndrome - FATHER’s is deleted (easy, willy = dick)
Angelman Syndrome - MOTHER’s is deleted.

Chromosome FIFTEEN.

Question 16

Why do maternal/paternal Ch. 15 deletions have different effects?

Answer 16

Because maternal and paternal Ch. 15 has different patterns of methylation, leading to differential expression between the two inherited chromosomes.

Question 17

What do inactivated Xs look like in metaphase?

Answer 17

Barr-bodies.

Question 18

How many genes do mitochondria have?

Answer 18

37.

Question 19

How many mitochondrial genes are for polypeptides?

Also how many for rRNA?

Answer 19

13 for polypeptides

2 for rRNA.

Question 20

Why can mutations in genes in nuclear DNA have an effect on functions within the mitochondria if the mitochondria have their own DNA?

Answer 20

Because the mitochondrial DNA only covers some of the polypeptide required for oxidative phosphorylation.
Mitochondria have 13, DNA has the other 74.

Question 21

What is the likelihood of a male passing on his mitochondrial DNA?

Answer 21

0%. Mitochondrial DNA is only passed down from the mother. The line stops at the son.

Question 22

Who are the only ones of my cousins that can pass on Gran’s mitochondrial DNA?

Answer 22

Eliza, Laura, Ingrid, Jenny, Savanna, Genevieve.

Question 23

Do I have any cousins once-removed that have Gran’s mitochondrial DNA?

Answer 23

No. Only Laura has a kid but he’s a male.

Question 24

What kinds of diseases are mitochondrial mutations associated with?

Answer 24

Muscular and neurological. ‘Unusual’ apparently.

Question 25

Why do mitochondria have higher mutation rates than nuclear DNA?

Answer 25

NO repair mechanisms.

Question 26

List 7 really familiar genetic diseases

Answer 26

``` Down's Huntington's Some MDs Albinism CF PKU Marfan PTEN Hamartoma syndromes ```

Question 27

List 4 less familiar (to you) genetic diseases

Answer 27

Fragile X Neurofibromatosis Osteogenesis imperfecta Tay-Sachs

Question 28

With SSA and CF it's fairly easy to assess risk of heredity. With others, inheriters will be "at risk" based on...

Answer 28

Family history and severity Population prevalence Gender (e.g. HH)

Question 29

4 diseases tested for in the newborn screening guthrie heel test

Answer 29

Congenital hyperthyroidism PKU Galactosaemia Cystic Fibrosis

Question 30

Two major methods are used for CARRIER SCREENING. They fall into:

Answer 30

Pedigree | Blood Tests - DNA probes for unexpressed recessive genes.

Question 31

Would you do a carrier screen for Huntington's Disease?

Answer 31

No. You know. It's autosomal dominant.

Question 32

What diseases do we have blood tests for to do carrier screening with?

Answer 32

SSA, CF, Tay-Sachs

Question 33

What genetic disease is treated with hormones?

Answer 33

Klinefelter's.

Question 34

What genetic diseases are treated by dietary restriction?

Answer 34

Phenylketonuria HH (iron) Wilson disease

Question 35

What's the most common CF mutation?

Answer 35

ΔF508

Question 36

If two CF carriers have a kid, what's the ratio of CF:carriers:non-carriers?

Answer 36

1:2:1

Question 37

What's the incidence of CF?

Answer 37

1/2500

Question 38

How many CF patients in Australia?

Answer 38

3000

Question 39

What's a meconium?

Answer 39

First crap a baby does.

Question 40

What's the FIRST clinical sign of CF?

Answer 40

Viscous meconium obstructs the ilium.

Question 41

What biomarker is used in the prick test for CF?

Answer 41

Immunoreactive trypsin- IRT (recall pancreatic blocking, build up and flooding of trypsinogen).

Question 42

Why can't we just do a universal DNA test for CF?

Answer 42

Because ΔF508, though the most common, it's only responsible for 2/3 of CF.

Question 43

When do we test for ΔF508?

Answer 43

After positive IRT screen from heel prick.

Question 44

What's the confirmatory diagnosis in this lecture for CF? | When is it done in 75% of cases?

Answer 44

Sweat test. 1yo. Bonus: 10% CF not diagnosed until 10yoa.

Question 45

What symptoms for CF are highlighted in this lecture?

Answer 45

Salty skin, Fatigue Coughing, wheezing, difficulty breathing Cyanosis

Question 46

For interest, they've listed for CF bulky, foul stools, cramps and weakness in hot weather due to sweating and...

Answer 46

retarded growth + delayed puberty.

Question 47

Where are the 4 loci encoding the gene for alpha Hb?

Answer 47

Chromosome 16

Question 48

ALPHA Thalassaemia: excess ___ chains in adult (and excess _____ chains in newborns)

Answer 48

ADULTS: beta NEWBORNS: gamma

Question 49

What's the aetiology of ALPHA thalassaemia?

Answer 49

Deletion on Chrom. 16 - too few alpha chains. | Excess-beta Hb molecule has abnormal dissociation curves.

Question 50

What regions is beta thal most prominant?

Answer 50

mediterranean and south asia | highest carrier frequency = maldives

Question 51

one idea of why beta thal might be so popular in south asia?

Answer 51

possibly protective against malaria

Question 52

RBC count is so high in beta thal that...

Answer 52

... a smear test is virtulally diagnostic.

Question 53

Symptoms of general thal? Make sense - RBC processing, yellow colour, HH, cause of HH and a liver thing.

Answer 53

Splenomegaly, jaundice, hyperactive bone marrow, haemochromatosis (esp heart iron deposits), hepatic sclerosis.

Question 54

Symptoms of beta thal specificlaly?

Answer 54

Sever anaemia (Cooley's) High serum bilirubin (and Fe) Enlarged marrow space.

Question 55

How many people in the world are supposed to have thalassaema?

Answer 55

60-80 million

Question 56

What measure is sometimes necessary in beta thal to calm down haemopoesis (and therefore haemochromatosis) ?

Answer 56

RBC hypertransfusions, esp. younger fractions. Otherwise, as few transfusions as possible.

Question 57

If hypertransfusion doesn't work, the patient may resort _______ if ________ also doesn't work.

Answer 57

Hypertransfusion Then iron chelation Then splenectomy.

Question 58

Haemophilia A B and C affect factors ........ respectively.

Answer 58

VII, IX, XI | Easy - sequence of odd numbers.

Question 59

What's basically an autosomal dominant haemophilia?

Answer 59

von Willebrand.

Question 60

When is haemophilia severe? I.e. spontaneous bleeding?

Answer 60

1% normal clotting factors or less.

Question 61

What's a particularly shitty (not just obviously bleeding) symptom that 90% of haemophiliacs have by around age 3-4?

Answer 61

Easy bruising = mega joint pain just from ambulation | Termed HAEMARTHROSIS

Question 62

Why did they have to stop using plasma to treat haemophilia? Including cryoprecipitated VIII-rich plasma?

Answer 62

Problems with HIV and Hep C transmission.

Question 63

Multiminicore has considerable overlap with _______ and _______ in terms of clinical and histological.

Answer 63

MD and spinal rigitity.

Question 64

What causes multiminicore? _________ apparent in the ________ represent areas of _____________ and _________.

Answer 64

Lightly-staining minicores; oxidative stain (histology) | low oxidative activity and mitochondrial paucity.

Question 65

What's the THM on MmD incidence?

Answer 65

Very rare. About 1/10 Congenital myopathies represent abotu 0.6/1000 births. In the UK and Sweden MMC disease is about 3.5-5.0 in 100,000.

Question 66

Gotta know this for some reason. | MmD is due to an autosomal ________ mutation of the _______ gene located at the locus:

Answer 66

Recessive Selenoprotein N 1p36

Question 67

To have MmD you can either be a SEPN1 homozygote or a compound heterozygote for _____. Ryan Reynolds is inbred. I don't like him.

Answer 67

RYR1. This one tends to be more common in cosanguineous families.

Question 68

SEPN1 tends to be pretty common for non-cosansuineous families, unlike _____

Answer 68

RYR1.

Question 69

Around how many pathological mtDNA mutations have been found?

Answer 69

250.