Genetics Flashcards

1
Q

what is genetic disease

A

an illness caused in whole or in part by an abnormality in the individual’s DNA, may be inherited or acquired

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2
Q

are genetic diseases familial

A

sometimes but not always

environmental disease can also be familial (ie transmittable diseases)

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3
Q

define congenital

A

present at birth

NOT genetic

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4
Q

are genetic diseases congenital

A

some but not always

an inherited disease is not always present at birth

environmental disease can be congenital

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5
Q

when can a familial disease be considered to be genetic

A

if large mendelian pedigree or if not, familial clustering, twin studies, adoption studies

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6
Q

what is familial clustering

A

familial clustering aims to show the closer the genetic relationship the higher the risk of disease bc the more shared genes= greater chance of that disease

h/e also share environment

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7
Q

what are twin studies

A

show differences in disease incidence (concordance rate) between MZ and DZ twins as share 100% vs 50% genes
genetically determined diseases show higher concordance MZ than DZ

h/e environment

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8
Q

adoption studies

A

whether shared genes or shared environment- ie does the adopted child have the disease?

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9
Q

what are diseases that affect onevs multiple genes called

A

single gene disease

polygenic disease

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10
Q

what are diseases of chromosomes called

what are diseases that involve many genes and the environment called

A

chromosomal disease

multifactorial disease

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11
Q

a disease of a germline cell leads to (and what is it)

A

(sperm/ova) an inherited condition

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12
Q

a disease of a somatic cell leads to

A

(body cells) non-inherited condition

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13
Q

single gene conditions vs complex diseases

A

single gene conditions are pathological mutations, present only in affected and carriers, significantly alter gene and its protein

complex diseases combination of normal variants present in everyone, subtly alter gene and protein,

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14
Q

how does risk of developing vary between single gene and complex diseases

A

more positive risk of developing if single gene disease
in complex diseases, genetic susceptibility factors in- ie how good or bad the versions of the gene are but lifestyle influences

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15
Q

PKT

A

phenyketonuria
autosomal recessive condition, both parents carriers
all tested at birth with Guthrie test
1 in 10000
disease arises due to lack of phenylaline hydroxylase
if know and do not eat phenylaline, no effects. if unaware and eat causes mental retardation, microcephaly, growth failure

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16
Q

karyotyping and normal karyotype

A

chromosomes are fixed in metaphase when chromosomes have condensed so visible

stain applied, banding used to identify chromosomal abnormalities as there is a unique regular pattern of banding for each chromosome

normal karyotype= 46XX or 46XY

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17
Q

what percentage of all conception have chromosomal abnormality

what percentage of first trimester miscarriages have chromosonal abnormality

A

7.5% all conceived have chromsomal abnormality

60% of 1st trimester miscarriages have chromsomal abnormality

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18
Q

how many chromsomes are in somatic vs germ cells, what are they otherwise called

A

somatic cells are diploid, have 46 chromosomes, so 2N.

germ cells (sperm and eggs) are haploid so 23 chromosomes

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19
Q

what is polyploidy

A

cells with chomsoms in multiples of N greater than 2N

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20
Q

what is aneuploidy

A

chromsomes NOT in multiples of N, ie missing or extra chromsome

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21
Q

What causes triploidy

A

Egg fertilised by 2 spermatozoa (dispermy) or by fertilisation of a diploid gamete that arises from failure of maturation

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22
Q

Aneuploidy and polyploidy are what type of chromosomal abnormality?

A

Numerical

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23
Q

What are the two outcomes of aneuploidy?

A

Trisomy of that chromosome or monosomy of that chromosome

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24
Q

What is a trisomy

A

An extra copy of that chromosome, ie downs is a trisomy of 21,,, trisomy 21

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25
Q

What is a monosomy

A

A loss of a copy of that chromosome is a monosomy of that chromosome

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26
Q

What type of aneuploidy is lethal

A

All complete monosomies of autosomal chromosomes 1-22 are lethal.
Partial monosomies may survive.

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27
Q

What is the only type of monsomy that is not lethal?

A

Monosomy X, Turner’s syndrome

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28
Q

What 2 things may aneuploidy result from

A

Non disjunction

Anaphase lag

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29
Q

What is non disjunction

A

Failure of chromosomes/sister chromatids to separate at anaphase in cell division

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30
Q

What is anaphase lag

A

Delayed movement of chromosomes after separation at anaphase

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31
Q

What does non disjunction in meiosis or mitosis result in?

A

One daughter cell with an extra copy (trisomy) and one daughter cell with a missing copy (monosomy)

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32
Q

What is the result of non disjunction in meiosis 1 and what happens at fertilisation

A

Meiosis 1 will have one cell with 4 copies of chromosome and one cell will have no copies of chromosome. (Instead of 2 each)

After meiosis 2, there will be 2 cells with 2 copies of the chromosomes and 2 cells with no copies of the chromosome

After fertilisation, 2 cells will be trisomy as sperm adds a chromosome and 2 cells will be monosomic

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33
Q

What happens when there is non disjunction of a chromosome in meiosis 2

A

1 cell will have 2 copies of chromosome, it’s partner cell will have no copies of chromosome. Next 2 cells will have one copy of chromosome each.

At fertilisation, the cell with 2 copies of chromosome will become trisomic, it’s partner cell will be monosomic, the next 2 cells will be disomic (normal)

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34
Q

What happens if there is non disjunction in meiosis 1 of chromosome 21 of oogenesis

A

After meiosis 1, one cell will have 4 X chromosomes, one cell will have no X chromosomes

After meiosis 2, first 2 cells will have 2 X chromosomes, next 2 cells will have no X chromosomes

At fertilisation, if an X is added, either of first 2 will become trisomic as 47XXX. Either of the second pair will be monosomic as 45X, Turners.

If a y is added, either of first pair will be trisomic as 47XXY, klinefelters, either of second pair will be monosomic as 45Y, this is lethal

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35
Q

45X is?

A

Turners syndrome

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36
Q

47XXY is

A

Klinefelter’s syndrome

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37
Q

Non disjunction of chromosome 21 in meiosis 1 of spermatogenesis results in

A

At meiosis 1, one cell will have 2X and 2Y, other cell will have none

After meiosis 2, one pair will have XY and one pair will have none

At fertilisation, both XY cells become 47XXY as klinefelters, both cells without will become 45X, turners

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38
Q

Non disjunction of chromosome 21 is more likely lethal in oogenesis or spermatogenesis?

A

Oogenesis

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39
Q

What happens if there is non disjunction of chromosome 21 in meiosis 2 of spermatogenesis

A

After meiosis 2 there will either:
be one XX chromosome and one without and next 2 cells will be Y and Y (normal)

At fertilisation, the XX cell will become 47XXX, next 45 X, next 2 normal XY

Or: after meiosis 2 there will be one cell YY, one cell without and 2 normal with an X each

After fertilisation there will be one XYY, one X and 2 normal xx

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40
Q

What is the only way 47XYY can arise

A

Non disjunction of meiosis 2 in spermatogenesis

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41
Q

What happens if non disjunction of chromosome 21 in mitosis happens early in post fertilisation?

A

A substantial proportion of cells will have trisomy 21 phenotype

How early this occurs influences how severe (early is severe)

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42
Q

Why do structural chromosomal abnormalities happen

A

Result from chromosomal breakage and usually involves 1 or 2 chromosomes

May be spontaneous, but rate is increased by exposure to mutagenic agents or inherited conditions with defects in DNA replication

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43
Q

What structural abnormalities may be seen in a single chromsome

A

Deletion
Inversion
Duplication
Isochromosome

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44
Q

Deletion is what? what type of chromosomal abnormality? occurs in how many chromosomes?

A

Deletion is a structural abnormality seen in a single chromosome

Deletion is the loss of part of a chromosome

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45
Q

Inversions are what? what type of chromosomal abnormality? occurs in how many chromosomes?

A

Inversions are structural abnormalities seen in a single chromosome

Inversions are the inversion of a segment of chromosome which may/may not involve the centromere

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46
Q

Duplications are what? what type of chromosomal abnormality? occurs in how many chromosomes?

A

Duplications are structural abnormalities seen in a single chromosome

Duplication of a chromosomal segment, in tandem or inverse configuration of original sequence

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47
Q

An isochromosome is what? what type of chromosomal abnormality? occurs in how many chromosomes?

A

An isochromosome is a structural abnormality seen in a single chromosome

An isochromosome is the duplication of 1 arm of that chromosome, coupled with the loss of the other arm, so there are 2 identical arms

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48
Q

What type of structural abnormalities would we see in 2 chromosomes

A

Insertions

Translocations- reciprocal or robertsonian

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49
Q

Insertions are what? what type of chromosomal abnormality? occurs in how many chromosomes?

A

Insertions are a structural abnormality seen in 2 chromosomes

Insertion is the breakage of material from 1 chromosome and insertion into another

50
Q

Translocation is what? what type of chromosomal abnormality? occurs in how many chromosomes?

A

Translocation is a structural abnormality, seen in 2 chromosomes

Translocation is the exchange of material between 2 chromosomes

51
Q

What is a reciprocal translocation

A

Reciprocal translocation is a structural abnormality seen in 2 chromosomes

Reciprocal translocation is the reciprocal exchange of material between chromosomes

52
Q

What is robertsonian translocation

A

Structural abnormality of 2 chromosomes

Only involve Acrocentric chromosomes (small arms are very short). The small arms are lost and the long arms of the 2 chromosomes join together

Leads to reduction by one chromosome

53
Q

Why do robertsonian translocations not have significant phenotypic effects

A

All important genes are in long arm of chromosomes

Though there will be issues when forming gametes

54
Q

Outcomes of a balanced reciprocal translocation in meiosis

A

Normal
Carrier of balanced translocation
Partial trisomy of 1 and partial monosomy of 1

55
Q

Outcome of meiosis in robertsonian translocation

A

Normal
Carrier if balanced translocation
Complete monosomy of 1 and complete trisomy of 1

56
Q

Phenotypic consequence of chromosomal abnormality in a single gene

A

Disrupt a single gene lead to loss of its product
Translocate the gene to a region of active chromatin domain so it is inappropriately expressed
Create a chimaeric gene that expresses an altered protein

57
Q

Phenotypic consequences of chromosomal abnormality in deletion of a small group of genes

A

If deletion of small group, phenotype due to lack of product of several genes (contiguous gene syndrome)

58
Q

Phenotypic consequence of abnormality of large regions or whole chromosomes results in

A

Phenotypic change
Severe birth defects including mental and growth retardation

Specific abnormalities largely due to dosage imbalance of only a few genes on that chromosome.

59
Q

Most common chromosomal causes of miscarriage?

A

Aneuploidy.
Aneuploidy so significantly disrupts cell eq not compatible with life mostly.

Trisomies represent 35% of miscarriages before 20 weeks

Complete autosomal monosomies lethal

60
Q

Monosomy 14, trisomy 14, monosomy 21 are

A

Lethal

61
Q

What is a balanced translocation

A

Even exchange of material with no genetic material being extra or missing

Correct amount genetic material present but not in normal pattern

62
Q

What is an unbalanced translocation

A

Exchange of material is unbalanced resulting in extra or missing material

63
Q

When does an unbalanced translocation occur

A

Fetid inherits a a chromosome with extra or missing genetic material from parent with balanced translocation (extra or missing bc parent has 2 of it where the other fills in the gaps)

64
Q

When are balanced chromosomal translocations identified

A

Subfertility leading to investigations
Raised risk result from combined test
Parental testing after child born with unbalanced

65
Q

How do balanced translocations affect risk of miscarriage

A

Increase risk.

66
Q

What happens when a balanced translocation carrier has children?

A

Balanced translocation carrier’s sperm or eggs have incomplete or partially duplicated sets of chromosomes

Tiny unbalanced structural abnormalities can affect many genes leaving severe effects on individual

May cause:
Fatal monosomy or trisomy
Normal chromosomes
Balanced translocation

67
Q

what are the types of chromosomal abnormality?

A

numerical-
aneuploidy
polyploidy

structural-
Deletion
Inversion
Duplication 
Isochromosome
Insertions
Translocations- reciprocal or robertsonian
68
Q

aside from chromosomal abnormality, what other type of dna abnormality is there?

A

molecular- gene level abnormality

69
Q

what types of molecular changes may we see in DNA

A

Point mutations, includes:

  • Truncating mutations
  • Non Truncating mutations

Promoter Methylation

70
Q

define point mutation

A

mutation affecting only one or very few nucleotides (bases) in a gene sequence

71
Q

Define truncating mutation

A

truncating mutation is a type of point mutation, whereby the wrong size protein or no protein product is made

72
Q

Define non-truncating mutation

A

non- truncating mutation is a type of point mutation, whereby there is a spelling mistake but an otherwise normal gene product

73
Q

in short, what is the difference between truncating and non truncating point mutations

A

truncating mutations= protein product wrong/ not made

non truncating mutation= protein functions

74
Q

what are the types of truncating mutations

A

nonsense mutation
frameshifting mutation
splice mutation

75
Q

what is a nonsense mutation

A

codon for an amino acid is replaced by a STOP codon

= ribosome stops mid protein synthesis

76
Q

what is a frameshifting mutation

A

deletions or insertions that alter the triplet reading frame

ie remove 1 codon and all others bump down one so meaning changes (or add one and all move up one)

beyond point of frameshifting mutation, doesn’t make sense as all shift by +/- 1

if 3 deleted may still make sense but not fully

often leads to early stop codon

77
Q

Outline splicing

A
exons= the coding bits
introns= junk sequences

exons are seperated by introns
when mRNA synthesised, introns are removed so only exons remain

there is a specific sequence at start and end of exons, recognised by splicing machinery

78
Q

what is a splice site mutation

A

mutation at splice sit leads to error in where spliced, may result in aboloshing a splice site or creation of a novel site

ie may keep an intron, may skip an exon, may splice early etc

79
Q

what are the types of non-truncating mutations

A

missense
silent
expansion of trinucleotide repeats

80
Q

what is a missense mutation

A

one AA is replaced with another

result depends on how different the new AA is and how important the original AA is for function of protein

81
Q

what is a silent mutation

A

mutation that does not result in replacement of one AA with another due to degeneracy in the code

82
Q

what is expansion of trinucleotide repeats

A

trinucleotide repeat sequences eg (CAG)n occur relatively frequently in genome

therefore may be okay, but if too many repeat sequences= unstable may cause disease

2 classes of trinucleotide repeats

83
Q

what is the first class of trinucleotide repeats?

A

genes with modest expansion of a particular trinucleotide repeat WITHIN CODING REGION

results in either

  • stable alleles= 10-30 repeats, no phenotypic change
  • unstable alleles= 40-200 repeats, eg huntingtons
84
Q

what is the other type of trinucleotide repeat mutations

A

genes with very large expansions of repeat sequences in NON CODING sequences

stable alleles= 5-50 repeats
unstable alleles= over 100, result in inhibition of gene expression or aberrant splicing

85
Q

what is the normal method for regulating expression of genes?

A

promoter methylation
gene transcription can be switched off by methylation of nucleotide bases, particularly cytosine in their promoter regions
this is how normally regulate expression of genes

86
Q

what is hyper/hypomethylation

A

a molecular abnormality, may occur pathologically (ie cancer)
hypermethylation= inappropriate switching off of affected gene
hypomethylation= inappropriate switching on of affected gene

87
Q

pathological mutation of nuclear DNA vs mitochondrial DNA

A

mutation of DNA=
mendelian inheritance,
wide range phenotypes,
wide range affected tissues

mutation of mitochondrial DNA=
maternal inheritance,
restricted phenotype as affects most energy consuming tissues
highly variable severity, depends how many mitochondria affected

88
Q

mutation in germ cell vs somatic cell

A

germ cell mutation= INHERITED mutation in DNA of egg or sperm, every cell of organism will be affected, can be passed onto offspring

somatic cell mutation= cannot be inherited. mutation in a single body cell, only tissues/cells that arise from this cell will be affected. No phenotype unless develops very early in development

89
Q

are there differences in the types of mutations seen in somatic vs germ cell mutations?

A

exact same mutations, but observed spectrum different

many mutations seen in somatic cells would be lethal if constitutional

most inherited germ cell mutations would have no observable consequences if only present in a few somatic cells

90
Q

when may somatic cell mutations be clinically significant in terms of phenotype

A

if occurs early in embryogenesis, significant proportion of clones of mutant cells, gives the cell a growth advantage so forms a tumour

91
Q

what does the outcome of mutation in DNA depend on?

A

depends where change is and how critical

if non critical then little to no effect

if critical then:
lack/reduced synthesis of protein
reduced or no protein function
altered protein function

92
Q

loss of protein function is usually associated with what type of inherited condition

A

recessive

93
Q

gain of protein function usually associated with what type of inherited condtion

A

dominant

94
Q

what does a square, circle and diamond mean on a pedigree chart

A
square= male
circle= female
diamond= unknown sex
95
Q

what does full shading, hashed shading, half shading mean on pedigree chart

A

full shading= affected
hash shading= don’t know
half shading= carrier

96
Q

eldest sibling is where on pedigree chart

A

to the left

97
Q

a single straight line connecting people vs a double straight line connecting people

A

single line= marriage

double line= consanguinous mating

98
Q

how does genetic disease result in phenotypic consequences

A

change in DNA= change in AA sequence= change in protein function= dysfunction

99
Q

why is it important to make diagnoses in genetic disorders

A

common cause child morbidity and hospitalisation (25% paeds patients have genetic disorder)
appropriate clinical management, treatment to improve prognosis if poss
info for family, risk estimation future offspring

100
Q

how do we identify genetic disorders

A

clinical presentation (some very clear, don’t need genetic testing)
family history and mendelian pedigree
genetic testing
some have blood markers etc

101
Q

tell me the most basic info about genes and inheritance of traits

A
2 genes (alleles are different versions of genes) for each trait
inherit one gene from each parent

may be homozygous- have two identical alleles, AA or aa

may be heterozygous, 2 different allels, Aa
in which case one will be:
Dominant: allele that is expressed, overrides the recessive
or
Recessive: hidden allele, not expressed
or have
Co-Dominance: both alleles are expressed

102
Q

what is segregation and independent assortment

A

segregation: for every gene, each parent contributes one of their alleles to offspring, so one allele from each

independent assortment: genes passed on in independent manner to other genes (except where linked traits, then genes will segregate as a unit)

103
Q

what are the characteristics of an autosomal dominant disorder

A

the mutant allele is dominant so only one mutant allele needed to cause disease

every affected child has an affected parent
vertical transmission
males and females affected equally
50% recurrence amongst children
normal children of affected parents will only have normal children

Aa= disease
aa= unaffected
104
Q

what are the characteristics of autosomal recessive disorders

A

2 mutant recessive alleles= disease

aa= affected
Aa= unaffected carrier

males and females affected equally
parents must both be carriers or one carrier one diseased
frequent in consanguity
horizontal inheritance- where one child affected likely see others in that family, but not seen in every generation

105
Q

if both parents are carriers, what is the probability of their children bein affected/not/ a carrier

A

25% normal
50% carrier
25% affected

106
Q

what are the characteristics of X linked recessive inheritance

A

MALES more affected
no male to male transmission
affected mother 100% has affected son
affected father 100% has carrier daughter

in males one copy of allele sufficient to cause disease as only have one X chromsome, in daughters would need 2 copies so males more affected

knights move transmission/ diagonal as usually carrier mother to afected son to carrier daughter and so on

107
Q

what are the characteristics X linked dominant

A

FEMALES more affected
no male to male transmission
affected father has 100% affected daughter
affected mum 50% affected son or daughter

108
Q

characteristics of Y linked inheritance

A

only father to son, never any females
dominant or recessive don’t apply as only one Y
seen in all male descendants

109
Q

characteristics of mitochondrial inheritance

A

only egg cells contribute mitochondria to embryo so only females can pass on
no male to male
female to son or daughter, maternal iniheritance
mother to all children

110
Q
what type of inheritance is this?
no male to male
affected mother 100% affected son
carrier mother 50% to son
affected father 100% carrier daughter
more males affected
A

x linked recessive

111
Q

what type of inheritance is this?
horizontal inheritance
males and females equally
affected child has carrier parent

A

autosomal recessive

112
Q

what type of inheritance is this
no male to male
maternal inheritance
mother to all children

A

mitochondrial

113
Q
what type of inheritance is this
no male to male
affected father 100% affected daughter
affected mum 50% chance to son or daughter
more females affected
A

X linked dominant`

114
Q

what type of inheritance is this?
only male to male
seen in all descendant males
never in females

A

Y linked

115
Q

what type of inheritance is this?
affected child has affected parent
males and females equally
vertical transmission

A

autosomal dominant

116
Q

if there is no male to male transmission, does every affected father have 100% affected daughters? yes vs no what is it

A

yes, X linked dominant
no, X linked recessive
no and every child of affected mum has it, mitochondrial

117
Q

does every affected child have an affected parent? yes vs no

A

yes, autosomal dominant sign

no, autosomal recessive sign

118
Q

if no male to male, does every affected mother have 100% affected son? yes vs no

A

yes, x linked recessive

no, x linked dominant

119
Q

what type of inheritance is it a sign of if
females affected more
males affected more

A

females more= X dominant

males more= X recessive

120
Q

the Smith family have one child with cystic fibrosis but the other 3 children are healthy, what is the chance that one of the other siblings is a carrier

A

know he isnt affected so
NO affected 25%
maybe carrier 50%
maybe normal 25%

therefore 2/3 chance carrier