Genetic Disorders

Question 1

what are the x4 classified genetic disorder categories?

Answer 1

mendelian disorders
multifactorial disorders
chromosomal (cytogenic) disorders
single gene disorders with non-classical inheritance

Question 2

define penetrance?

Answer 2

amount of people that carry an autosomal dominant gene and expressing trait

Question 3

define variable expressivity?

Answer 3

variable expression of autosomal dominant trait in effected individuals

Question 4

define codominance?

Answer 4

full expression of both alleles of a given gene pair in a heterozygote

Question 5

define polymorphism?

Answer 5

multiple allelic forms of a single gene

Question 6

define pleiotropism?

Answer 6

multiple end effects of a single mutant gene

Question 7

define genetic hertogeneity?

Answer 7

production of a given trait by different mutations at multiple loci

Question 8

what can occur during replication of DNA?

Answer 8

point mutations

= abnormality of a short protein chain

Question 9

what can a mutation involve?

Answer 9

loss of single nucleotide base

loss of whole gene

addition of single nucleotide base

substitution of one nucleotide base of another base

Question 10

in regard to Mendelian disorders what is commonly transmitted as autosomal dominant?

Answer 10

mutations in structural genes

Question 11

in regard to mendelian disorders what is familial hypercholesterolemia caused by?

Answer 11

mutation in the gene for a membrane receptor

Question 12

what is the characteristic features of autosomal dominant disorders?

Answer 12

defect in structural proteins therefore STRUCTURAL PROBLEM

age of onset is delayed

high variable expressibility + low penetrance

affects both men and women

Question 13

what is the risk to a child of an autosomal dominant disorder?

Answer 13

50%

Question 14

what is an example of a CNS autosomal dominant disorder?

Answer 14

neurofibromatosis
Huntingtons disease

Question 15

what is an example of a urinary autosomal dominant disorder?

Answer 15

polycystic kidney disease

Question 16

what is an example of GIT autosomal dominant disorder?

Answer 16

familial polyposis coli

Question 17

what is an example of a skeletal autosomal dominant disorder?

Answer 17

marfans syndrome
elhers-danlos syndrome
osteogenesis imperfecta

Question 18

what is an example of a metabolic autosomal dominant disorder?

Answer 18

familial hypercholesterolaemia

Question 19

what is an example of haem autosomal dominant disorder?

Answer 19

Von willebrand disease
hereditary spherocytosis

Question 20

what gene is affected in familial hypercholesterolaemia?

Answer 20

chromosome 19

Question 21

what is the characteristic features of autosomal recessive disorders?

Answer 21

enzyme proteins affected - therefore FUNCTION

age of onset is early

low variable expressibility, high penetrance

Question 22

what are points to note re: inheritance of autosomal recessive conditions?

Answer 22

affected person usually unaffected parents (carriers)

both parents have transmitted the disease

usually birth of an affected child = first indication of disease in family

25% risk if a prior child has been affected

Question 23

what is an example of a CNS autosomal recessive disorder?

Answer 23

freidreich ataxis
spinal mucular atrophy

Question 24

what is an example of a metabolic autosomal recessive disorder?

Answer 24

cystic fibrosis
alpha-1 antitrypsin deficiency

Question 25

what is an example of a storage problems autosomal recessive disorder?

Answer 25

wilsons disease haemochromatosis glycogen storage disease lysosomal storage disease

Question 26

what is an example of a endocrine autosomal recessive disorder?

Answer 26

congenital adrenal hyperplasia

Question 27

what is an example of a haem autosomal recessive disorder?

Answer 27

thalassemias sick cell anaemia

Question 28

what are traits of sickle cell anaemia?

Answer 28

abnormal Hb is synthesised there is only mild likelihood of vascular occlusions

Question 29

who is affected in recessive x-linked disorders?

Answer 29

all males affected 50% for females

Question 30

who is affected in dominant x-linked disorders?

Answer 30

both females and males are affected

Question 31

what are all sex-linked disorders?

Answer 31

x-linked almost all are recessive

Question 32

how may females be affected in x linked recessive disorders?

Answer 32

if father is affected and mother is carrier or if x-inactivation is female skewed

Question 33

what is there none of in x-linked recessive disorders?

Answer 33

no male to male transmission

Question 34

what is the risk of disease in a child of an affected mother in x-linked dominant disease?

Answer 34

50% regardless of sex

Question 35

what is the risk of disease in a child of an affected father in x-linked dominant disease?

Answer 35

all his daughters will be affected none of his sons will be

Question 36

what are examples o X-linked recessive disorders?

Answer 36

duchennes muscular dystrophy haemophilia A+B diabetes insipidus fragile x syndrome

Question 37

what occurs in a case of a woman who is heterozygous for a recessive X-linked disorder?

Answer 37

disorder may be partially expressed

Question 38

what diseases are found specifically on the X chromosome?

Answer 38

glucose 6 phosphate dehydrogensase deficiency haemophilia A+B NOT FAMILIAL POLYPOSIS COLI

Question 39

the possession of an x chromsome in excess of the normal complement is less harmful than the possession of an extra autosome because of what?

Answer 39

because only one x chromosome in a cell is functional

Question 40

what are multi-factorial disorders?

Answer 40

combined effects of 2 or more mutant genes + environmental factors

Question 41

what are examples of multi-factorial disorders?

Answer 41

DM gout hypertension coronary heart disease

Question 42

in regards to multi-factorial diseases - what is the risk of recurrence in subsequent pregnancies?

Answer 42

less than 10%

Question 43

in regards to multi-factorial diseases what is the risk in identical twins?

Answer 43

20-40% concordance

Question 44

in regards to multi-factorial disease what is the risk of recurrence of the disorder in first degree relatives?

Answer 44

2-7%

Question 45

what are the characteristics of a multi-factorial disorder?

Answer 45

disease occurs more frequently in children of an affected person than among grandchildren risk of developing disease is greater if both parents are affected disease occurs more frequently in women than in men

Question 46

how to cytogenetic disorders occur?

Answer 46

changes in number of chromosomes changes in structure of chromosomes

Question 47

what are conditions which are usually associated with chromosomal translocation?

Answer 47

chronic myeloid leukaemia burkitts lymphoma

Question 48

why are karyotype abnormalities thought to be a primary event in development of many human neoplasms?

Answer 48

because in certain types of human neoplasia, karyotype abnormalities is non-random and common in that tumour type

Question 49

what are the most common non-random structural abnormalities in tumour cells?

Answer 49

balanced translocations chromosomal deletions cytogenetic manifestations of gene amplifications

Question 50

what is aneuploidy?

Answer 50

refers to a chromosome number different from the normal

Question 51

how can aneuploidy be detected>?

Answer 51

karyotyping

Question 52

how can aneuploidy be detected in tumour cells?

Answer 52

flow cytometry

Question 53

what are the facial characteristics of down syndrome?

Answer 53

oblique palpebral fissure epicanthic folds

Question 54

what is the risk of congenital heart malformation in down syndrome?

Answer 54

40% death during infancy otherwise life span not reduced

Question 55

what is the risk of developing leukaemia in down syndrome?

Answer 55

10-20 fold

Question 56

what is there a significant risk of if surviving >35 years in downs syndrome?

Answer 56

premature alzheimers

Question 57

what causes down syndrome?

Answer 57

95% free trisomy therefore meiotic non-dysfunction 5% translocation (robertonsian)

Question 58

what is kleinfelters syndrome?

Answer 58

male hypogonadism 2 or more X chromosomes at least one Y chromosome (e.g. 47, XXY)

Question 59

what are the clinical features of klinefelters syndrome?

Answer 59

male infertility failure of male secondary characteristics atropic testis elevated FSH + oestrogen

Question 60

what is the clinical features of turners syndrome?

Answer 60

short stature neck skin folds lymphoedema increased carrying angle of arm IG and life span normal

Question 61

what occurs in utero in 99% of those suffering with turners syndrome?

Answer 61

abort

Question 62

what is turners syndrome?

Answer 62

moscaism with respect to sex chromosomes not likely to be due to a balanced reciprocal translocation

Question 63

what is the gene abnormality in angelmans syndrome?

Answer 63

genomic imprinting

Question 64

what is the gene abnormality in cystic fibrosis?

Answer 64

deletions

Question 65

what is the gene abnormalities in osteogenesis imperfecta>

Answer 65

gonadal moscaiscm

Question 66

what is the gene abnormality in beta thalassaemia?>

Answer 66

deletions

Question 67

what is the gene abnormality in fragile X syndrome?

Answer 67

triple repeat mutations

Question 68

what type of technique is very sensitive to finding HIV>

Answer 68

polymerase chain reaction

Question 69

what does the technique of southern blot involve?

Answer 69

separation of dna sequences according to size may be used to detect abnormalities due to point mutations

Question 70

what does fluorescence in situ hybridisation (FISH) enhance and identify?

Answer 70

enhances karyotyping can identify intragene deletion