Flashcard Set Preview
| Side A | Side B | ||
| 1 |
how many children are born with a congenital abnormality
|
5%
|
|
| 2 |
Name 4 types of genetic disorders
|
Single-gene defects
mitochondrial disorders
chromosomal imbalances
multifactorial - genetic...
|
|
| 3 |
What are the 2 most common types of genetic disorders
|
Autosomal
X-linked
|
|
| 4 |
What are autosomal recessive mutations caused by
|
Caused by mutations that result in loss of functional gene
product eg, insertions, deletions,...
|
|
| 5 |
On what chromosome is the cystic fibrosis gene
|
chromosome 7
|
|
| 6 |
What protein does the cystic fibrosis gene normally produce
|
cystic fibrosis transmembrance conductance regulator
|
|
| 7 |
What is the most common defect that causes CF
|
Deletion of 3 nucleotides from the gene - normally pheny alanine
|
|
| 8 |
At what position on the chromosome is the phenylalanine amino acid normally located in CF
|
Delta F508 on the long arm on chromosome 7
|
|
| 9 |
What is the normal role of the CFTR
|
They are in specialised endothelial cells and regulate the passage of Cl- through the cell....
|
|
| 10 |
What type of inheritance is cystic fibrosis
|
Autosomal recessive
|
|
| 11 |
What is the prevalence of CF
|
1in2000
|
|
| 12 |
What is consanguinity and why is it a problem
|
Partners share at least one ancestor (in the recent past),
or - both parents descended from...
|
|
| 13 |
What are the chances that one allele present in one partner is also present in the other partner...
|
0.5
|
|
| 14 |
Give an example of a disease and the population who have a high incidence of recessive disease
|
Old order Amish - ellis -van creveld syndrome. Because founded by just 50 couples.
|
|
| 15 |
In consangunious mating a child who is homozygous for a recessive allele, who may he have inherited...
|
Both maybe from his great -grandfather or great -grandmother
|
|
| 16 |
What is the probability of inheriting a recessive allele
|
1/2 or 0.5
|
|
| 17 |
How do yo u calculate the probability of inheriting an allele from a relative
|
1/2 for each descendent multiplied. 0.5*0.5*0.5 see picture
e.g. for inheritance from a great...
|
|
| 18 |
What is the inbreeding co-efficient
|
The inbreeding coefficient = 4 * 1/2 (to the power of how many people e.g. great grand parent...
|
|
| 19 |
What is the inbreeding coefficient of the child if the parents are: sibling, half siblings,...
|
1/4
1/8
1/8
1/16
1/32
|
|
| 20 |
Define: autosomal dominant
|
Disorders result from mutations which, unlike those responsible for recessive disorders,...
|
|
| 21 |
Name a disease that the majority of the time is caused by new mutations
|
Acondroplasia (very short legs) is caused by new mutations 7/8ths of the time
|
|
| 22 |
Define: penetrance
|
The percentage of carriers of a specific dominant allele that show the relevant phenotype.
or
the...
|
|
| 23 |
Describe retinoblastoma
|
It is an autosomal dominant disease - 10% of retinoblastoma populationare obligate carriers...
|
|
| 24 |
Give an example of a gene which has age dependent penetrance
|
Huntington's disease
|
|
| 25 |
On what choromose is the Huntington's gene
|
Chromosome 4
|
|
| 26 |
What is Huntington's disease due to
|
Trinucleotide CAG repets, the larger the number of CAG repeats the younger the onset of huntington's
|
|
| 27 |
What would be a normal number of CAG repeats, what would be an inconclusive number of...
|
Normal - <35
Inconclusive - 36-39
Disease - >40
|
|
| 28 |
What does CAG code for
|
Glutamine
|
|
| 29 |
On what arm is the gene located
|
Short arm
|
|
| 30 |
Define anticipation in genetics
|
Disease occurs at an earlier age as it is transmitted through the pedigree, it occurs when...
|
|
| 31 |
What is variable expression and give an example disease
|
Variation in clinical features (type and severity) of a genetic disorder between individuals...
|
|
| 32 |
What is neurofibromatosis 1
|
A common disorder of the nervous system, eyes and skin (cafe au lait spots) 1/3500
|
|
| 33 |
What is the difference in disease between people with homozygosity and heterozygosity for achondroplasia
|
There can be a difference in symptoms in heterozygotes for a condition e.g. In achondroplasia...
|
|
| 34 |
Is sickle cell trait dominant or recessive
|
dominant
|
|
| 35 |
What is fragile x?
|
X-linked disorder, excessive expansion of CCG in the FMR1 gene. Seen in males twice as often...
|
|
| 36 |
what is x chromosme inactivation
|
x-chromosome inactivation is where one x-chromosome can inactivate in a female (also called...
|
|
| 37 |
What is a germline mosaic?
|
mosaic of mutated and normal cells
|
|
| 38 |
Name a disease that can occur from germline mosaics
|
Duchenne muscular dystrophy - occurs from a germline mosaic in 15% of cases.
|
|
| 39 |
What is duchenne muscular dystrophy
|
There is no detectable dystrophin causing muscle weakness. 1in3300 males. X-linked recessive...
|
|
| 40 |
What is mitochondrial inheritance
|
THe mitochondrial DNA is inherited soley from the mother
|
|
| 41 |
Name some diseases which occur from mitochondrial mutations
|
Leber hereditary optic neuropathy (retinalregeneration)
|
|
| 42 |
What are the 5 main types of mutation
|
Deletions, insertions, single base substitutions, frameshift and dynamic mutations
|
|
| 43 |
What are the 3 types of single base substitutions?
|
missense (amino acid replacement), nonsense (premature stop codons), splice site
|
|
| 44 |
What is an example of dynamic mutations
|
trinucleotide repeats eg CAG
|
|
| 45 |
What are the major consequences of mutations
|
Loss of function or gain in function
|
|
| 46 |
When does loss of function occur
|
Normally occurs in recessive traits but can occur in some dominant traits e.g. Haploinsufficiency...
|
|
| 47 |
Whe does gain in function occur
|
Dominant traits e.g. huntington's disease
|
|
| 48 |
Is cystic fibrosis gain or loss of function
|
loss of function
|
|
| 49 |
describe cystic fibrosis
|
Recessive therefore only manifests when have 2 mutant alleles, gene codes for the CFTR protein....
|
|
| 50 |
WHy is there a wide spectrum of disease in CF
|
Due to genotype-phenotype correlations. Wide spectrum of disease, ranging from very mild and...
|
|
| 51 |
To get a positive sweat test in CF what level of CFTR function must you be below
|
<5%
|
|
| 52 |
What is the most common CF allele
|
deltaF508
|
|
| 53 |
What is PKU
|
Loss of function, recessive.
Sever learning difficulties,
fair skin, eczema, epilepsy
•...
|
|
| 54 |
Define a missense mutation
|
A missense mutation is a single base pair substitution resulting in a change in the amino acid...
|
|
| 55 |
Define a nonsense mutation
|
A nonsense mutation results in a premature stop codon, which ends the translation of the mRNA...
|
|
| 56 |
Define a frameshift muation
|
Frameshift mutations occur when the number of deleted or inserted base pairs is NOT a multiple...
|
|
| 57 |
Define an inframe mutation
|
In-frame mutations occur when the number of deleted or inserted base pairs IS a multiple of...
|
|
| 58 |
What is a phenotype
|
Some allelic variation results in an observable difference, or a phenotype. A phenotype is...
|
|
| 59 |
Define homozygous and heterozygous
|
A heterozygous individual is someone who has two different alleles at a locus. For instance,...
|
|
| 60 |
In a pedigree what is a proband
|
A proband is identified by an arrow pointing towards the symbol for that individual. The proband...
|
|
| 61 |
Where are PAH mutations
|
On exon 7 . 450 different mutations. most individuals with PKU are heterozygotes, it is a mixture...
|
|
| 62 |
what is haploinsufficiency
|
in most situations having one copy of a gene is enough. In some situations it is not - haploinsufficiency....
|
|
| 63 |
Give and example of a disease which results from haplo-insufficiency
|
Waardenburg syndrome type 1 - autosomal dominant inheritance, haplo-insufficiency,
|
|
| 64 |
What is waardenburg syndrome type 1
|
– caused by mutations in PAX3 gene, a DNA-binding transcription that is expressed in the...
|
|
| 65 |
Give an example of a dominant gene which has loss of function
|
osteogenesis imperecta, it is a dominant negative, the product of the mutant gene intereferes...
|
|
| 66 |
What is osetogenesis imperfecta type II
|
perinatal form, it is lethal, get flattened vertebral bodies, large unmineralised skull, short...
|
|
| 67 |
What is osteogenesis imperfecta
|
inability or deficiency of type 1 collagen, due to an amino acid substitution to glycine,
severe...
|
|
| 68 |
Name a gain of function disease
|
Autosomal dominant, huntington's disease
|
|
| 69 |
Describe huntington's disease
|
• Autosomal dominant
• Progressive neurodegenerative disease
• Strikes in middle...
|
|
| 70 |
Name another gain of function disease
|
Charcot-marie-tooth disease,
|
|
| 71 |
Describe charco-marie-tooth
|
most common inherited peripheral neuropathy in the world• slow progressive degeneration of...
|
|
| 72 |
What is the difference between heterozygosity and homozygous for the charcot-marie-tooth disease
|
more severe disease in homozygous for the mutation
|
|
| 73 |
For monogenci traits what other factors can modify the phenotype
|
environmental - e.g. PKU and glucose-6-phosphate dehydrogenase deficiency (get chronic...
|
|
| 74 |
name 4 types of genetic testing
|
prenatal screening, newborn screening, carrier testing, diagnostic screening, presymptomatic...
|
|
| 75 |
why is early recognition important
|
it may allow reversal of the disease process, prevent the disease occuring through informed...
|
|
| 76 |
What are 3 important considerations when deciding whether to screen
|
THe disease itself - is it a severe disease, is it common, is there treatment availableTHe...
|
|
| 77 |
What are the 2 types of prenatal screening and give examples of each
|
Invasive - amniocentesis, chorionic villus sampling, cordocentesis, preimplantation genetic...
|
|
| 78 |
Describe amniocentesis
|
done in the second trimester in weeks 15-17Risk of fetal loss is ~0.5% above background riskcultured...
|
|
| 79 |
Describe chorionic villus sampling
|
Done in 1st trimester weeks 10-11, risk of fetal loss 1-1.5% above background risk, cultured...
|
|
| 80 |
Describe newborn screening of PKU
|
within 1st week of life, biochemical assay on blood sample or guthrie test (measuring...
|
|
| 81 |
Name 3 diseases we do carrier screening for
|
CF, Tay-sachs, beta-thalassemia
|
|
| 82 |
name 3 diseases that we do pre-symptomatic screening for
|
huntington's disease, familiar breast cancer, hereditary non-polyposis colorectal cancer
|
|
| 83 |
describe some of the ethical issues surrounding genetic testing
|
Genetic testingPrenatal diagnosis, especially for nondisease traits or sexTesting for genes...
|
|
| 84 |
what is the human karyotype
|
the human karyotype is 46 chromosomes - this comprises of 2 sex chromosomes and 22 pairs of...
|
|
| 85 |
how are the autosomes labelled
|
they are labelled 1 to 22 according to their size
|
|
| 86 |
what is the chromosome structure?
|
3 billion base pairs, coiled around histones to pack tightly to form chromosomes, majority...
|
|
| 87 |
how does this coiling occur
|
The DNA is wound around histones to form a structure that looks like beads on a string, this...
|
|
| 88 |
waht is the structure of a chromosome
|
short arm = p armlong arm = q armsisterchromatids held to gether at centromeretelomeres protect...
|
|
| 89 |
What are the chromosome abnormalities
|
aneuploidy - too many or too few chromosomesstructural abnormalities - which may be balanced...
|
|
| 90 |
what are the 2 balanced arrangements and what are the 2 unbalanced arrangements
|
balanced - translocations and inversionsunbalanced - deletions and duplications
|
|
| 91 |
why does aneuploidy occur
|
mostly from miotic non-dysjunction, it offten occurs in meiosis 1 stage in females which starts...
|
|
| 92 |
what are the stages of meiosis
|
replication, synapsis, recombinations, dysjunction, and meiosis |
|
| 93 |
what does meosis non-dysjunction create?
|
disomic and nullisomic gametes |
|
| 94 |
If a disomic or nullisomic gamete fuses with a normal gamete or a nullisomic gamete waht...
|
trisomic conceptus, monosomic conseptus or uniparental disomy
|
|
| 95 |
What is the genetics behind Down's syndrome
|
Majority are primary trisomy 21- 95%. This is either 47XX+21 or 47XY+21They can also be due...
|
|
| 96 |
what are robertsonian translocations
|
Formed by
the fusion of two acrocentric chromosomes (13, 14, 15,
21,and 22).Long arm and...
|
|
| 97 |
who has the risk of having a child with a translocation disease
|
balanced carriers
|
|
| 98 |
name some diseases which can occur due to translocations
|
patau syndrome,recurrent miscarrigaesdown's dyndromwmale infertility
|
|
| 99 |
what is an accrocentric centromere?
|
an acrocentric centromere, partitioning the chromosome into a large arm containing the...
|
|
| 100 |
what do alternate and adjacent translocations produce
|
 Adjacent 1 segregation occurs when adjacent chromosomes with... |
|
| 101 |
describe a down's translocation
|
strong family history of down's, 45,XX, der(14;21)(q10;10)more likely to be a maternal carrier,
|
|
| 102 |
what is edwards syndrome
|
Mental disability – severe
Dysmorphic – micrognathia, prominent occiput
Clenched...
|
|
| 103 |
what are the genetics behind edwards
|
1:3000
live births
1:500
at age maternal 43
Primary
trisomy 18 47,XX,+18 or
47,XY,+18...
|
|
| 104 |
what is patau syndrom
|
Mental disability – severe
Dysmorphic – cleft lip, cleft palate, holoprocencephaly,...
|
|
| 105 |
what are the genetics behind patau syndrome
|
1:5000
live births
1:1100
at maternal age 43
Primary
trisomy 13 &
translocation...
|
|
| 106 |
what is turner's syndrome
|
Normal intelligence
Dysmorphic – webbed neck, broad chest with widely spaced nipples
Primary...
|
|
| 107 |
what are the genetics behind turners
|
1:5000
live births, normal lifespan
No
maternal age effect, 80% are paternal in origin
99%
abort...
|
|
| 108 |
what is kleinfelters syndrome
|
•47XXY or 47XXY/46XYIncidence = 1/1000
•Usually taller than average
•Disproportionately...
|
|
| 109 |
Aneuploidy for the autosomes is lethal except for which chromosomes
|
13, 18, 21
|
|
| 110 |
Explain X inactivation
|
Females have 2 x chromosomes, one in mostly surplus to requirements therefore inactivated,...
|
|
| 111 |
What are the structural choromosome abnormalities
|
Robertonian translocations, reciprocal translocations, insertions, deletions, ring chromosomes,...
|
|
| 112 |
what is a reciprocal translocation
|
transfer between two non-homologous chromosomes, 1in500, balanced carriers are normally phenotypically...
|
|
| 113 |
Discuss deletions
|
terminal or interstitiallarge deletions are 4p, 5p, q11, q18e.g. Angelman/prader willi
|
|
| 114 |
Describe 2 deletions synderomes
|
wolf-hirschorn - 4p - severe mental disability, frontal bossing, hypertelorism, carp shaped...
|
|
| 115 |
what are submicroscopic deletions
|
sub-microsopic - only detectable by FISH, genetic testing done following clinical diagnosis,...
|
|
| 116 |
name 5 submicroscopic deletionis
|
cri du chatprader wiliangelman syndromewolf-hirschornwilliams syndrome
|
|
| 117 |
what is williams syndrome
|
1in10,000deletion on long arm of chromosome 7interstistial proximal deletion7q11.3deletion...
|
|
| 118 |
what is angelman syndrome
|
severe mental disability,absent speechmovement disorderhappy disposition, inappropriate laughterseizuresopen...
|
|
| 119 |
what is prader willi
|
moderate learning difficultieshypotoniafailure to thrivehypogonadismobseityshort staturesmall...
|
|
| 120 |
how are angelman and prader wili assocaited
|
same mutation mechanism in chromosome 1515q11-q13different expression depending on parental...
|
|
| 121 |
why do you get uniparental disomies
|
due to meiosis non dysjunctioneither - anapahse 1 or sisterchromatids in meisosis 2then undergoes...
|
|
| 122 |
what is cytogenetic testing
|
the study of the constitution of cells through visualisation and analysis of chromosome
|
|
| 123 |
what samples can you use for cytogenetic testing
|
prenatal - amniotic fluid, fetal blood lymphocytes, chroinic villuspostnatal - peripheral blood...
|
|
| 124 |
what cytogenetic tests can you do
|
g-banding - using metaphase chromosomes, FISH, QF-PCR, MLPA, rapid tests on uncultured cells
|
|
| 125 |
what is g-banding
|
requires culturing metaphase chromosomes and synchronising them all, takes time
|
|
| 126 |
what is the gold standard genetic tests
|
chromosome analysis - takes ages, but only way to look at whole chromosome for both balanced...
|
|
| 127 |
what is FISH and how is it done
|
flourescent in situ hybridisationmolecular cytogenetic techniquedifferent types of probe with...
|
|
| 128 |
what isFISH used for
|
rapid prenatal diagnosismicrodeletion testingsubtelomere testinglooking for structural abnormalities
|
|
| 129 |
what is rapid prenatal diagnosis
|
75% done coz screening tests suggest abnormalityfull karyotype takes 2 weeks coz cells must...
|
|
| 130 |
what is interphase chromosome enumeration
|
used in rapid prenatal diagnosis - uncultured cells, will only detect certain aneuploidies,...
|
|
| 131 |
what is the future of cytogenetics
|
lab automationmicro arraysthe end of g-banded chromosome analysis
|
|
| 132 |
what are microarrays
|
looks at whole genomeat greater resolution than normal cutogeneticslike fish but with loads...
|
|
| 133 |
what is the cgh chip in microarrays
|
arragy comparative genomic hybridization (looks for chromosome imblance)take control dna and...
|
No comments yet! Be the first to add a comment below!
Please login to post comments.
After login, we will forward you back to this flashcard.