Genetic Testing and Non-Mendelian Inheritance Flashcards
Define
Cambridge reference sequence
the mitochondrial DNA sequence first sequenced in 1981. It was used as a basis for comparison with mtDNA test results until it was replaced with the Reconstructed Sapiens Reference Sequence (RSRS)
How many gene in the mtDNA specify all the RNA products required for synthesising mt proteins?
24
Define
Maternal serum tests
a test that measures several substances in the blood of a pregnant woman in the second trimester of pregnancy. The results can be used to determine the risk that the baby has a chromosome disorder or neural tube defect such as spina bifida
What tests are offered to women of advanced maternal age?
Amniocentesis or CVS
What does imprinting involved?
Imprinting involved a region of DNA being differentially methylated in eggs and sperm
Define
Imprinted genes
genes whose expression is determined by the parent that contributed them
Definition
A test that combines a number of different measures together to provide an estimate of the chance that a pregnancy is affected by a chromosome condition, such as Down syndrome.
Combined first-trimester screen
Definition
an extranuclear double-stranded DNA found exclusively in mitochondria that in most eukaryotes is a circular molecule and is maternally inherited
Mitochondrial DNA
What is an example of a newborn screening test?
Phenylketonuria screen via heel prick
Both the mutations and the heteroplasmy of a mitochondrial disease appear to evolve with _______________ within an individual
time
Define
Matrilineal
of or based on kinship with the mother or the female line
What non-invasive methods can be used in pre-natal diagnosis?
Ultrasound
Maternal serum tests
Non-invasive prenatal screening
Definition
a protein produced by a fetus which is present in amniotic fluid and the bloodstream of the mother. Levels of the protein can be measured to detect certain congenital defects such as spina bifida and Down’s syndrome
Alpha-fetoprotein (AFP)
A dextral dd female water snail and a dextral DD male are crossed. What is the phenotype and genotype of the offspring?
Sinistral; Dd
Define
Screening
The examination of a group of usually asymptomatic individuals to detect those with a high probability of having or developing a given disease
What is the preferred invasive technique before 15 weeks?
Chorionic villus sampling
Define
Nuchal translucency
a collection of fluid under the skin at the back of your baby’s neck. The amount of fluid is measured during an ultrasound scan: between 11 weeks and 14 weeks of pregnancy
Definition
a diagnostic imaging technique based on the application of ultrasound. It is used to see internal body structures such as tendons, muscles, joints, blood vessels, and internal organs
Ultrasound
Definition
a location within nuclear DNA or the D-loop of mitochondrial DNA in which base pairs of nucleotides repeat (in the case of nuclear DNA) or have substitutions (in the case of mitochondrial DNA)
Hypervariable regions
How many genes in the mtDNA encode polypeptides?
13
How is amniocentesis performed?
- A needle is inserted into the amniotic sac
- Amniotic fluid is sampled
- Foetal cells are tested using genetic tests
- Biochemical analysis of the amniotic fluid can also be used (e.g. alpha-fetoprotein)
Definition
The examination of a group of usually asymptomatic individuals to detect those with a high probability of having or developing a given disease
Screening
What test is used to determine nuchal translucency?
Ultrasound
Define
Chorionic villus sampling
a test made in early pregnancy to detect congenital abnormalities in the fetus, in which a tissue sample is taken from the villi of the chorion
What are three examples of non-Mendelian inheritance?
- Extranuclear inheritance
- Maternal effect
- Imprinted genes
The heavy strand of mtDNA is rich in which nucleotide? What about the light strand?
Heavy = guanosine
Light = cytosine
Define
Heteroplasmy
the presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual
Define
Cytogenetics
the study of inheritance in relation to the structure and function of chromosomes
Definition
the mitochondrial DNA sequence first sequenced in 1981. It was used as a basis for comparison with mtDNA test results until it was replaced with the Reconstructed Sapiens Reference Sequence (RSRS)
Cambridge reference sequence
Which two organelles have their own chromosomes/genomes?
Mitochondria
Chloroplasts
How is mtDNA inherited?
Matrilineally (i.e. from mother)
Definition
a new genetic test that uses cell-free circulating fetal DNA in the maternal serum to screen for the more common fetal aneuploidies: trisomy 21 (Down syndrome), trisomy 18 (Edward syndrome), trisomy 13 (Patau syndrome) and monosomy X (Turner syndrome)
Non-invasive prenatal testing
Define
Amniocentesis
a process in which amniotic fluid is sampled using a hollow needle inserted into the uterus, to screen for abnormalities in the developing fetus
Define
Non-invasive prenatal testing
a new genetic test that uses cell-free circulating fetal DNA in the maternal serum to screen for the more common fetal aneuploidies: trisomy 21 (Down syndrome), trisomy 18 (Edward syndrome), trisomy 13 (Patau syndrome) and monosomy X (Turner syndrome)
Non-invasive prenatal testing uses free circulating _________ in the maternal serum to screen for the more common ____________
Foetal DNA; foetal aneuploidies
A female plant with variegated leaves is crossed with a green leafed male. What is the phenotype of the offspring?
Green, white or variegated offspring
Definition
refers to the redox reactions involving the flow of electrons along a series of membrane-bound proteins, coupled with the generation of Adenosine triphosphate (ATP). Also known as oxidative phosphorylation
OXPHOS
Define
Mitochondrial DNA
an extranuclear double-stranded DNA found exclusively in mitochondria that in most eukaryotes is a circular molecule and is maternally inherited
Why is mtDNA useful in forensics?
- Barring mutation, mtDNA of siblings and all maternal relatives is identical
- Due to the high copy number, mtDNA is particularly advantageous in cases where amount of extracted DNA is very small, or degraded
When is prenatal diagnoses performed?
- There is a family history
- Previous child has a chromosomal abnormality
- Parents have a chromosomal abnormality
- Family history of a genetic disorder
- They have been tested as carriers
- Increasing maternal age
- Risk of neural tube disorder
- Abnormal results from ultrasound
- Routine screening test
How does heteroplasmy arise?
Mutation
What is the chorion?
A part of the placenta that derived from the embryonic tissue (mesodermal connective tissue and trophoblastic cells of the placenta)
What are problems and considerations with DNA testing?
- Not all genetic diseases have a known gene
- The specific gene causing the disease in this family must be known
- The specific allele causing the disease in this family must be known
- Some alleles can give different severity in different individuals
- Some disorder show variable penetrance
- Severity of mitochondrial disorders is hard to predict because of heteroplasmy
- Trinucleotide repeat disorders can also be difficult to interpret
Define
Chromosome microarray
a DNA-based method of genetic analysis, which can identify clinically significant chromosome abnormalities that are below the resolution of conventional chromosome analysis. Microarray analysis can be performed on prenatal diagnostic samples, peripheral blood, and products of conception
How are mitochondrial diseases managed?
Prenatal diagnosis
Preimplantation genetic diagnosis
Use of donor oocytes:
- Cytoplasmic transfer
- Nuclear transfer
Define
Hypervariable regions
a location within nuclear DNA or the D-loop of mitochondrial DNA in which base pairs of nucleotides repeat (in the case of nuclear DNA) or have substitutions (in the case of mitochondrial DNA)
What does maternal serum testing detect?
Neural tube defects
Define
Nuclear transfer
a form of cloning. The steps involve removing the DNA from an oocyte (unfertilised egg), and injecting the nucleus which contains the DNA to be cloned
What can complicated chorionic villus sampling?
Mosaicism
Define
Clinical utility
whether the test can provide information about diagnosis, treatment, management, or prevention of a disease that will be helpful to a consumer
What is the best way to study hypervariable regions 1 and 2?
PCR
What in the maternal serum is an indicator of neural tube defects?
High levels of alpha-fetoprotein
Definition
a form of cloning. The steps involve removing the DNA from an oocyte (unfertilised egg), and injecting the nucleus which contains the DNA to be cloned
Nuclear transfer
What clinical features are typical of mitochondrial diseases? How many do you need for a mitochondrial disease to be considered?
Unusual combination of >2 symptoms:
- Combinations of neurological signs
- Encephalopathy
- Dementia
- Ataxia
- Dystonia
- Neuropathy
- Seizures
- Myopathic signs
- Hypotonia
- Weakness
- Cardiomyopathy
- Deafness
- Diabetes
- Retinal pigementation
- Acidosis
True or False:
Maternal extranuclear inheritance is the only extranuclear inheritance possible
False
It is usually maternal, however can also see biparental or paternal inheritance (much rarer)
What is included in the combined first trimester screen (cFTS)?
Nuchal translucency and maternal serum testing
Why is invasive prenatal diagnosis testing only conducted on high risk preganancys?
There is some risk of miscarriage
What is the explanation for maternal effect inheritance?
During maturation, the oocyte is surrounded by maternal nurse cells for nutrient supply. The maternal effect genetic products of the nurse cells are transported into the oocyte to assist with embryogenesis. So the genotype of the nurse cells influence the phenotype of the offspring
True or False:
There are no introns in mtDNA
True
What is the homeoplasmic mutation?
When every mitochondrial genome carries causative mutations
Definition
whether the test can provide information about diagnosis, treatment, management, or prevention of a disease that will be helpful to a consumer
Clinical utility
How is chorionic villus sampling performed?
- Needle through cervix or through abdomen
- Biopsy of tissue from the villous area of the chorion
If the fluid at the back of a developing baby’s neck is thicker than normal what can that indicate?
Down syndrome
Definition
the presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual
Heteroplasmy
What are the problems with using mtDNA in forensics>
- Nuclear DNA typing has greater discriminatory power
- mtDNA analysis cannot distinguish between individuals related on the maternal line
- Most useful if sample is unsuitable for nuclear DNA testing
Definition
a stochastic process that increases cell-to-cell mutant DNA loads variability
mtDNA bottleneck
Definition
a test result which wrongly indicates that a particular condition or attribute is absent
False negative
Definition
a DNA-based method of genetic analysis, which can identify clinically significant chromosome abnormalities that are below the resolution of conventional chromosome analysis. Microarray analysis can be performed on prenatal diagnostic samples, peripheral blood, and products of conception
Chromosome microarray
True or False:
Majority of babies born with Down syndrome have younger mothers
True
What cytogenetics are carried out on cells from amniocentestis or CVS?
- Karyotyping using G-banded metaphase spreads
- Fluorescent in situ hybridization (determine number of chromosomes)
Define
Preimplantation genetic diagnosis (PGD)
a procedure used prior to implantation to help identify genetic defects within embryos. This serves to prevent certain genetic diseases or disorders from being passed on to the child
What invasive tests can be used in prenatal diagnosis?
Amniocentesis
Chorionic villus sampling
Shell coiling in the water snail (dextral/sinistral) is an example of what mode of inheritance?
Maternal effect
Definition
how well the genetic variant being analyzed is related to the presence, absence, or risk of a specific disease
Clinical validity
Define
Endosymbiosis
symbiosis in which one of the symbiotic organisms lives inside the other
Definition
a group of birth defects in which an opening in the spinal cord or brain remains from early in human development
Neural tube defect
Definition
a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother
Maternal effect
What are the disadvantages of non-invasive prenatal testing?
- Analysis restricted to chromosomes 13, 18, 21 (and in some cases X and Y) but atypical chromosomal abnormalities account for 30% of all abnormal karyotypes
- Small proportion of women are not able to get a determinate NIPT result (low fetal fraction)
- High cost
- Positive result requires invasive testing before action is taken
Definition
of or based on kinship with the mother or the female line
Matrilineal
Define
Maternal effect
a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother
Definition
a test result which wrongly indicates that a particular condition or attribute is present
False positive
Where are hypervariable regions found in the mtDNA?
Small section of triple-stranded DNA due to repeat synthesis of a short segment of H strand DNA or ‘D loop’
Definition
a term used in genetics to describe a eukaryotic cell whose copies of mitochondrial DNA are all identical. In normal and healthy tissues, all cells are homoplasmic
Homoplasmy
Define
False negative
a test result which wrongly indicates that a particular condition or attribute is absent
Why does mtDNAs higher mutation rate compared to the nuclear genome make it useful to explore human evolution?
- Easy to efficiently assay diversity in many samples
- Polymorphisms are easier to find
Define
mtDNA bottleneck
a stochastic process that increases cell-to-cell mutant DNA loads variability
Define
False positive
a test result which wrongly indicates that a particular condition or attribute is present
A male plant with variegated leaves is crossed with a green leafed female. What is the phenotype of the offspring?
All green
What properties do mitochondria/chloroplasts share with bacteria?
- Circular chromosomes
- No nucleus or histones
- Same form of RNA polymerase to transcribe genes
- Divide by simple fission
Which non-invasive techniques are available to younger mothers to screen for trisomys?
Maternal serum tests
Ultrasound
Definition
the study of inheritance in relation to the structure and function of chromosomes
Cytogenetics
Definition
a test made in early pregnancy to detect congenital abnormalities in the fetus, in which a tissue sample is taken from the villi of the chorion
Chorionic villus sampling
Define
Clinical validity
how well the genetic variant being analyzed is related to the presence, absence, or risk of a specific disease
Definition
an assisted reproductive technique in which an ovum, removed from the intended mother, is injected with cytoplasm from the ovum of a different donor, who is generally younger; the treated egg is then inseminated and returned to the uterus of the mother
Cytoplasmic transfer
Definition
the transmission of genes that occur outside the nucleus. It is found in most eukaryotes and is commonly known to occur in cytoplasmic organelles such as mitochondria and chloroplasts or from cellular parasites like viruses or bacteria
Extranuclear inheritance
What are the advantages of non-invasive prenatal testing?
- No risk to the pregnancy
- Highly sensitive screening test for Down syndrome
What does the endosymbiosis theory state?
Mitochondria and chloroplasts derived from symbiotic bacteria that initially lived inside cells of ancestors of all eukaryotes (mitochondria), and ancestors of green algae and plants (chloroplasts)
What percentage of mtDNA is coding?
93%
True or False:
Mitochondrial gene products are exported and used in several different parts of the cell
False
Genes encode products that function within the organelle
What is chromosome microarray?
The primary tool for evaluation of intellectual disability and structural malformations in infants and children. It allows for the detection of small deletions and duplications at a much higher resolution than karyotyping. However, needs expert interpretation and is expensive and hence only offered after consultation with specialist physicians
Define
Alpha-fetoprotein (AFP)
a protein produced by a fetus which is present in amniotic fluid and the bloodstream of the mother. Levels of the protein can be measured to detect certain congenital defects such as spina bifida and Down’s syndrome
Definition
a test that measures several substances in the blood of a pregnant woman in the second trimester of pregnancy. The results can be used to determine the risk that the baby has a chromosome disorder or neural tube defect such as spina bifida
Maternal serum tests
Define
Ultrasound
a diagnostic imaging technique based on the application of ultrasound. It is used to see internal body structures such as tendons, muscles, joints, blood vessels, and internal organs
Define
Extranuclear inheritance
the transmission of genes that occur outside the nucleus. It is found in most eukaryotes and is commonly known to occur in cytoplasmic organelles such as mitochondria and chloroplasts or from cellular parasites like viruses or bacteria
Definition
symbiosis in which one of the symbiotic organisms lives inside the other
Endosymbiosis
Define
Cytoplasmic transfer
an assisted reproductive technique in which an ovum, removed from the intended mother, is injected with cytoplasm from the ovum of a different donor, who is generally younger; the treated egg is then inseminated and returned to the uterus of the mother
Definition
a procedure used prior to implantation to help identify genetic defects within embryos. This serves to prevent certain genetic diseases or disorders from being passed on to the child
Preimplantation genetic diagnosis (PGD)
Why is genomic imprinting considered an epigenetic effect?
The alteration of the DNA or chromatic is not actually a change in the sequence of the DNA
Definition
a collection of fluid under the skin at the back of your baby’s neck. The amount of fluid is measured during an ultrasound scan: between 11 weeks and 14 weeks of pregnancy
Nuchal translucency
Definition
a process in which amniotic fluid is sampled using a hollow needle inserted into the uterus, to screen for abnormalities in the developing fetus
Amniocentesis
True or False:
Different mitochondria with different DNA sequences can co-exist within the cytoplasm of a cell
True
The pigmentation genes in 4 o’clock plants are found in the chloroplasts. A female, white plant crosses with a male, green plant. What colour will the offspring be?
All white
Why is mtDNA a pathogenic hotspot even though it is a small target?
- 93% of mtDNA is coding - higher chance of functional mutation
- Many more rounds of replication - more chance for errors
- Ho histone protection for mtDNA - substantial oxidative damage
- mtDNA lacks adequate DNA repair mechanism - mutation cannot be repaired
What is a heteroplasmic mutation?
When there is a mixed population of normal and mutant mitochondrial genome
True or False:
Imprints are passed onto offsrping
False
The imprint remains throughout the life of the mammal but is then erased during the production of their gametes and not passed on
Define
Combined first-trimester screen
A test that combines a number of different measures together to provide an estimate of the chance that a pregnancy is affected by a chromosome condition, such as Down syndrome.
Define
Neural tube defect
a group of birth defects in which an opening in the spinal cord or brain remains from early in human development
Define
Homoplasmy
a term used in genetics to describe a eukaryotic cell whose copies of mitochondrial DNA are all identical. In normal and healthy tissues, all cells are homoplasmic
What does a prenatal test provide?
- A choice to terminate the pregnancy if the child is going to have a severe genetic disorder
- Better planning for pre-natal care, or management of condition after birth
- Psychological preparation for the parents
- Re-assurance that the child is no affected
What is the name of the sequence that mtDNA is compared to?
Anderson/Cambridge/Oxford sequence
Define
OXPHOS
refers to the redox reactions involving the flow of electrons along a series of membrane-bound proteins, coupled with the generation of Adenosine triphosphate (ATP). Also known as oxidative phosphorylation
Definition
genes whose expression is determined by the parent that contributed them
Imprinted genes
How many genes do human mitochondria contain?
37
