CS&B - Genetics - Cytogenetics; Inheritance; Genomics Flashcards
What term refers to the patterns of inheritance of single gene disorders that are passed from parent to child as autosomal recessive, autosomal dominant, X-linked recessive, and X-linked dominant diseases?
Mendelian inheritance
What does it mean for a disease’s inheritance to be multifactorial?
It is likely a combination of multiple genes and the environment
What are some examples of non-Mendelian single gene inheritance patterns?
Certain trinucleotide repeats;
mitchondrial inheritance
Define locus (genetic).
The anatomical position of a gene on a chromosome
How many alleles can a single gene locus have?
Many
What is a single nucleotide polymorphism?
A change in an allele
How many genes exist in the human genome?
~30,000
One mitotic chromosome is basically two ____________s connected by a _____________.
Chromatid;
centromere
What letter denotes the short arm of a chromatid?
What letter denotes the long arm of a chromatid?
p;
q
What is the six nucleotide repeating sequence of a telomere?
TTAGGG
What do satellite stalks of acrocentric chromosomes contain?
Nucleolar organizer regions (NORs)
note: sites of ribosomal RNA (rRNA) genes
Describe chromosomes according to the following terms:
metacentric
submetacentric
acrocentric
What part of acrocentric chromosomes contains the nucleolar organizer regions (NORs)?
What do these regions do?
Satellite stalks;
code for ribosomal RNA (rRNA)
What is the proper notation for a euploidic female?
What is the proper notation for a male with an extra Y chromosome?
What is the proper notation for a female with Turner’s syndrome?
46,XX;
47,XXY;
45,X0
What umbrella term refers to a change in chromosomal number in one chromosomal pair (e.g. monosomy, trisomy)?
What umbrella term refers to an increase in chromosomal number in all chromosomal pairs (e.g. triploidy, tetraploidy)?
Aneusomy;
polyploidy
How does FISH relate to chromosomal analysis?
Targets a specific locus of interest
How do microarrays relate to chromosomal analysis?
Can detect losses or gains up to 1 kb
True/False.
G-banding (and other staining methods) can be used in differing resolutions to show either routine numbers of bands (~400) or high numbers of bands (~750).
True.
What type of chromosomal translocation does not result in any loss of genetic material?
A balanced translocation
What type of chromosomal translocation results in a loss of genetic material?
An unbalanced translocation
Is a microarray likely to detect balanced rearrangements?
Is a microarray likely to detect mosaicism?
No;
no
What chromosomal analysis technique is useful for identifying very large deletions?
What chromosomal analysis technique is useful for identifying very small deletions?
What chromosomal analysis technique is useful for identifying a single locus of interest?
G-band karyotyping;
microarrays;
FISH
What are the three main types of genetic probes?
Single gene;
repeating sequences;
chromosome-spanning
What type of genetic analysis involves comparing thousands of patient genes to thousands of control genes?
Microarrays
The terms co-dominance, recessive, dominant, and incomplete dominance are referring to what genetic category?
The genotype-phenotype relationship
Name the inheritance pattern being described:
disease does not skip generations,
male and female progeny each have a 50% risk of inheriting the disease,
male-to-male vertical transmission does occur
Autosomal dominant
Name the inheritance pattern being described:
two germline mutations to develop disease,
equally transmitted by men and women,
disorder often only appears in a single generation
Autosomal recessive
What chance do two carriers of a disease that is purely autosomal recessive have of passing it on to their child?
25%
What is genetic penetrance?
The percentage of those that have the genotype that also have the clinical phenotype
What explains this pedigree chart?
Incomplete penetrance
What is expressivity in regards to a genetic disorder?
The same genotype can have differing phenotyped
What is locus heterogeneity in regards to genetic disorders?
Different mutated genes (and even modes of inheritance) result in the same phenotype
What is allelic (intralocus) heterogeneity in regards to genetic disorders?
Different mutations within a single gene result in the same disorder
Name the inheritance pattern being described:
incidence much higher in males,
no father-to-son transmission,
female carriers may show variable expressivity
X-linked recessive
To which sex of his children will a man with an X-linked dominant disease pass the disease?
To which sex of her children will a woman with an X-linked dominant disease pass the disease?
To all his daughters;
to any of her children (male and female)
Who is more likely to have an X-linked dominant disease, men or women?
Women
(because they can receive it from both parents; men can only receive it from their mothers)
As you look at an pedigree chart for the transmission of a certain disease, you notice that the disease is present in each generation, and there is no male-to-male transmission of the disease.
What is the inheritance pattern?
X-linked dominant
What is the inheritance pattern for this disease?
X-linked dominant
What does it mean for a disease to be sex-limited?
It is transmitted autosomally but only expressed in one sex
What is an example of co-dominance in humans?
What is an example of incomplete-dominance in flowers?
Blood type;
red flower + white flower = pink flower
What notation would signifiy the probability of ‘x’ happening?
P(x)
What notation would signifiy the probability of ‘x’ and‘y’ happening?
P(x)*P(y)
What notation would signifiy the probability of ‘x’ or‘y’ happening?
P(x) + P(y)
What notation would signifiy the probability of ‘x’ not happening?
1 - P(x)
How can autosomal dominant disorders be differentiated from X-linked dominant disorders via a pedigree chart?
The X-linked dominant will NOT show male-to-male transmission
What are some examples of Mendelian inheritance?
What are some examples of chromosomal aneuplodies?
What are some examples of non-Mendelian inheritance?
Autosomal dominant or recessive, X-linked dominant or recessive;
numerical increases or decreases (nullisomy, monosomy, trisomy,), Robertsonian translocations, copy number variants (triploidy, tetraploidy);
mitochondrial, trinucleotide repeats
What are some examples of Mendelian inheritance?
Autosomal dominant or recessive, X-linked dominant or recessive
What are some examples of chromosomal aneuplodies?
Numerical increases or decreases (nullisomy, monosomy, trisomy,),
Robertsonian translocations,
copy number variants (triploidy, tetraploidy)
What are some examples of non-Mendelian inheritance?
Mitochondrial, trinucleotide repeats
Inheritance for most common diseases is said to be:
Multifactorial
(due largely to an undetermined combination of multiple genes and environmental factors)
Autosomal recessive
Autosomal recessive
Autosomal dominant WITH reduced penetrance
Mitochondrial
For an autosomal recessive disease, what is the risk for two carrier parents to have a child with the illness?
For an autosomal recessive disease, what is the risk for two carrier parents to have a child that is just a carrier for the illness?
For an autosomal recessive disease, what is the risk for two carrier parents to have a child without the illness and that is not a carrier?
25%
50%
25%
For an asymptomatic individual whose sibling has an autosomally recessive disease and whose parents do not, what is the individual’s likelihood of being a carrier for the disease?
2/3
(Both parents are carriers;
if the individual had the disease, we’d know;
that only leaves three options, two of which where the individual is a carrier)
For an asymptomatic individual whose sibling has an autosomally recessive disease and whose parents do not, what is the individual’s likelihood of being a carrier for the disease?
What is the individual’s likelihood of having a child with the disease?
2/3;
2/3 * the risk that their partner is a carrier
What is the genetic term for a disorder in which the abnormal genotype does not always display the disease phenotype?
Reduced penetrance
A mutation with 95% penetrance would show the diseased phenotype in what percentage of individuals with the disease genotype?
What percentage of individuals with the diseased genotype would show no clinical signs or symptoms?
95%;
5%
What is the genetic term for a disease genotype(s) that shows varying ‘levels’ of disease severity in its phenotypes?
(I.e., not everyone with the diseased genotype has the same severity of S/Sy)
Variable expressivity
What are the two types of genetic heterogeneity?
Allelic (intralocus) heterogeneity;
locus (interlocus) heterogeneity
Define genetic heterogeneity.
Different genetic loci produce phenotypes that are clinically indistinguishable
Multiple alleles at the same gene locus cause the same disease phenotype. What term describes this situation?
Allelic (intralocus) heterogeneity
Individual genotypes at multiple loci can all independently cause the same disease phenotype. What term describes this situation?
(I.e. multiple genes at multiple loci can all cause the same clinical presentation)
Locus heterogeneity
What genetic term describes the occurrence when a single gene affects multiple phenotypic characteristics?
Pleiotropy
What increases your chance of developing a multifactorial disease?
Your closeness in a pedigree chart to affected relatives
True/False.
All females are technically mosaics.
True
(due to Lyonization)
The genetically different cell lines in a mosaic individual must arise from what common structure?
Must the divergence be pre- or postnatal?
A common zygote;
either
What is uniparental disomy?
One parent supplies both chromosomes in a pair to the child.
Can mosaicism occur as late as during tissue differentiation?
Yes
What is somatic mosaicism?
What is gametic mosaicism?
Mosaic cells mixed throughout the body or in different tissues;
mosaicism in the gametes only
Besides reduced penetrance or a new mutation, what else could explain this pedigree chart if is showing an autosomal dominant disorder?
Gametic mosaicism in the father
What causes genetic anticipation (such as in Huntington’s disease)?
Expanding trinucleotide repeats through generations
How can an individual be a ‘carrier’ for trinucleotide repeat disorders?
They can have an elevated number of repeats, putting their offspring at greater risk depending on both the other parent’s number of repeats and the number of new repeats made during fertilization
Recessively inherited disorders are usually which: a loss of enzyme function or a change in bodily structure?
Loss of enzyme function
Dominantly inherited disorders are usually which: a loss of enzyme function or a change in bodily structure?
A change in bodily structure
What term describes the presence of multiple mitochondrial DNA variants in an individual?
Heteroplasmy
Is reduced penetrance usually associated with recessively or dominantly inherited disorders?
Dominant
If a syndrome’s genetic cause is unclear and a physician has exhausted attempts to identify a related gene, what may be a ‘shotgun’ option?
Genome-wide association searches
(although expensive and labor intensive)
Are most breast and ovarian cancers familial?
No
(they are often new mutations and/or isolated cases)
What genetic term refers to the situation where a child gets both chromosomes in a pair from one parent?
Uniparental disomy
Via what steps should you approach this question?
1. Write down the Hardy-Weinberg equations
(p + q = 1 ; p2 + 2pq + q2 = 1)
2. Solve for q (q2 is the number of homozygotes for this autosomal recessive disease –> in this case 1 per 40,000)
3. Solve for p –> (1 - q) (in this case, 1 - 0.005)
4. Find carrier rate, 2pq –> (2*0.995*0.005 = ~1 per 100)
Answer = 1 per 100
Via what steps should you approach this question?
1. Determine the mother’s risk of being a carrier (2/3 as she has an affected sibling)
2. Determine the father’s risk of being a carrier
2a. Write down the Hardy-Weinberg equations
(p + q = 1 ; p2 + 2pq + q2 = 1)
2b. Solve for q (q2 is the number of homozygotes for this autosomal recessive disease –> in this case 1 per 2,500)
2c. Solve for p –> (1 - q) (in this case, 1 - 0.02)
2d. Find carrier rate, 2pq (2*0.98*0.02 = ~1 per 26)
3. Multiply the parents’ risks together (1/26 * 2/3)
4. Multiply the new risk by 1/4 (for the child’s risk of having the disease if both parents are carriers) (0.0064 * 1/4)
Answer = 1 per 150
Robertsonian translocations involve what type of chromosome?
Why?
Acrocentric chromosomes;
the p arms can be lost with little-to-no effect on phenotype
Which are the acrocentric chromosomes?
13, 14, 15, 21, 22
In the fertilization of gametes that come from a cell with a Robertsonian translocation of chromosomes 14 and 21, how many of the potential zygotes will be normal?
How many will be balanced carriers?
How many will miscarry?
How many will have Down syndrome?
1;
1;
2 (if born, the monosomy 21 will likely not live long);
1
In the fertilization of gametes that come from a cell with a Robertsonian translocation of chromosomes 14 and 21, how many of the potential zygotes will be completely genetically normal in regards to chromosomal number?
1
In the fertilization of gametes that come from a cell with a Robertsonian translocation of chromosomes 14 and 21, how many of the potential zygotes will be balanced carriers?
1
In the fertilization of gametes that come from a cell with a Robertsonian translocation of chromosomes 14 and 21, how many of the potential zygotes will miscarry?
Why?
2;
due to trisomy 14 and monosomy 14
(NOTE: the monosomy 21 zygote is not likely to live long past birth)
In the fertilization of gametes that come from a cell with a Robertsonian translocation of chromosomes 14 and 21, how many of the potential zygotes will have Down syndrome?
1
What genetic analysis tool(s) can be used to detect large deletions and/or duplications, translocations, and even chromosomal mosaicism?
Karyotyping
What genetic analysis tool(s) should be used when you have a specific gene in mind for which you want to check?
FISH
(Fish for the specific one)
(e.g. Cri-du-Chat or DiGeorge syndromes)
What genetic analysis tool(s) should be used when you have multiple genes to check all at once?
Microarray
What characteristic is common to autosomes 13, 14, 15, 21, and 22?
The are acrocentric chromosomes
(very short p arms that are easily lost in translocations)
A young woman of northern European descent is the single parent of a child with autosomal recessive cystic fibrosis. She marries her first cousin and becomes pregnant. What is the probability that her child will have cystic fibrosis?
1/32
The parent of this woman through whom she is related to her first cousin has a 1/2 chance of carrying the mutant CF,
this parental sib has a 1/2 chance of carrying the allele and this person’s child (the first cousin) also has a 1/2 chance of carrying the mutant allele.
Cumulative risk = 1/2 x 1/2 x 1/2 = 1/8 that the first cousin has a mutant allele.
Then the risk to have an affected child is 1 x 1/2 x 1/8 x 1/2 = 1/32.
The family below is segregating the mutant allele for disease X, a very rare genetic disorder inherited in an autosomal recessive pattern, with 100% penetrance. II-2’s first wife delivers an affected child, but dies in childbirth. II-2 later marries his first wife’s half-sister (II-3), and she becomes pregnant. What is the chance that this child will be affected?
1/16
(1/2 * 1/2 * 1/4)
A man and a woman, each of whom has autosomal recessive congenital deafness, have four biological children, each of whom has normal hearing.
What genetic term could likely explain this outcome?
Locus heterogeneity
(different autosomally recessive genes causing their similar disease presentations)
True/False.
In X chromosome inactivation, all of the X chromosome genes are inactivated.
False.
(Examples: Short arm, X chromosome genes which are not inactivated are the Xga antigen gene and the steroid sulfatase gene. Some long arm, X chromosome genes are needed to maintain ovarian function until menopause.)
True/False.
Robertsonian translocations usually involve metacentric chromosomes.
False
(acrocentric)
Prader-Willi syndrome (PWS) can result from either an interstitial deletion involving the paternal copy of chromosome subregion 15q1-q13 or from maternal uniparental disomy of chromosome 15.
The reason for this is:
The maternal copy of the gene(s) responsible for PWS is imprinted and is not expressed.
In Prader-Willi syndrome, which copy of the specific gene on chromosome 15 is imprinted?
What does this mean?
The maternal gene is imprinted AND thus inactivated
In Angelman syndrome, which copy of the specific gene on chromosome 15 is imprinted?
What does this mean?
The paternal gene is imprinted AND thus inactivated
What are two different kinds of epigenetics?
DNA, chromatin
What is the main form of epigenetics found in humans?
Methylation of CpG domains
(specifically methylating the cytosine)
Besides methylation of CpG domains, what other epigenetic modifications are common in human genomes?
Chromatin modifications
(e. g. histone acetylation, phosphorylation, and methylation)
(e. g. non-coding RNA histone-binding sequences)
Which aspect of epigenetics is associated with cancer development, increased methylation or decreased methylation of DNA sequences?
Increased methylation
What does deamination of cytosine produce?
What does deamination of 5-methylcytosine produce?
Uracil;
thymine
5-methylcytosine is involved in what branch of genetics?
Epigenetics (DNA methylation)
What is a CpG island?
Unmethylated CpG-rich sequences at the promoters and 5’ ends of contitutively active genes
Methylating a CpG island has what effect on its constitutively active gene?
Gene silencing
Are CpG island promoters generally methylated or not methylated?
Not
(a few specific ones are hypermethylated in certain cancers)
What process results in genetic imprinting?
DNA methylation
(and subsequent gene silencing)
Carcinogenesis is associated with hypermethylation of what?
Certain CpG promoter islands
What genes are associated with the mismatch repair system?
MLH1, MLH2
What is the term for the probability/likelihood of a heritable disease found in a family to be found in more members of the family (e.g. the chance of a new baby having the disease)?
Recurrence risk
Explain the ‘CpG’ notation in CpG island.
(NOTE: turn phone sideways for answer)
5’ Cytosine - phosphodiester bond - Guanine 3’
3’ Guanine - phosphodiester bond - Cytosine 5’
What is the usual immediate purpose of histone methylation?
What is the usual immediate purpose of CpG methylation?
What is the end result of both?
Preventing histone acetylation;
HDAC recruitment;
gene silencing
What does it mean for two genes to be ‘linked?’
The genetic loci are close together on the same chromosome;
they tend to NOT follow independent assortment
What percentage of newborns will have a birth defect?
~5%
