Genetics Flashcards
Remind yourself of what a deletion chromosome disorder is
State an example
- Portion of chromosome missing
- Cri du chat (missing portion of chromosome 5)
Remind yourself what a duplication chromosome disorder is
State an example
- Portion of chromosome is duplicated
- Charcot-Marie-Tooth (short arm of chromosome 17)
State and briefly describe three types of translocation
- Reciprocal translocation: portion of one chromosome is swapped for another; occurs between two homologous chromosomes
- Non-reciprocal translocation: portion of one chromosome leaves first chromosome and attaches to another without any exchange taking place; occurs between two homologous chromosomes
- Robertsonian translocation: occurs in acrocentric chromosomes 13, 14, 15, 21 & 22 (these have a long arm which has most of genetic info and a short arm containing little genetic info). Lose short arm completely and the two long arms connect at centromere. Lose a chromosome. Phenotypically normal but have 45 chromosomes leading to problems in offspring
Remind yourself what a trisomy chromosome disorder is
State some examples
- Person has three copies of a particular chromosome
- Examples:
- Down’s syndrome: trisomy 21
- Edwards syndrome: trisomy 18
- Patau syndrome: trisomy 13
Remind yourself what mosaicism is
cells of the body have different numbers or arrangements of chromosomes. For example, if an individual has mosaic trisomy 18, this means that some of the cells have three copies of chromosome 18 while other cells have two copies of chromosome 18.
Mutation occurs after conception.
Mitochondrial disorders are common; true or false?
False; rare
State some examples of problems mitochondrial disorders can cause
- Myopathies (due to poor production of ATP)
- Rare forms of:
- Deafness
- Blindness
- Diabetes mellitus
- Epilepsy
Where is DNA in mitochondria stored?
How is the DNA in mitochondria arranged?
- Mitochondria have own DNA separate from cell nucleus; found in matrix of mitochondria
- Arranged in a circle
Mitochondrial disorders are caused by maternal inheritance; explain how mitochondrial disorders show maternal inheritance
- At conception, sperm enters egg and DNA of both nuclei combine
- Mitochondria in sperm is found in the tail which doesn’t enter the egg
- Hence, father doesn’t contribute to any mitochondria in zygote (and hence the fetus and child)
- Mitochondrial DNA is from mother
- However, must consider that not all mitochondria in mother’s cells will be affected; the proportion of affected mitochondria that are passed on to offspring will determine whether individual is affected
What is diagnostic genetic testing?
State an example
- Testing fetus or person for a suspected genetic condition
- E.g. Down’s syndrome, Turner syndrome
What is predictive testing?
State an example
- Testing a person for a specific mutation that has implications for them in the future
- E.g. BRCA1 breast cancer gene
What is carrier testing?
State an example
- Testing patient or potential/future parents for the gene for a specific autosomal recessive condition to calculate risk of passing it to their children
- E.g. cystic fibrosis
Karyotyping, microarray testing, specific gene testing & DNA sequencing are examples of genetic tests we can do. Describe karyotyping
- Need mitotically dividing cells as obtain chromosomes from metaphase spread
- Look at number, size and structure of chromosomes
- Helpful in e.g. Down’s syndrome, Turner syndrome
Karyotyping, microarray testing, specific gene testing & DNA sequencing are examples of genetic tests we can do. Describe microarray testing
Cut up genetic material from individual using enzymes. Different genes have different molecular weights. Apply cut up genetic material to a plate that separates molecule of different weights into different locations allowing you to see what genes person expresses.
For example, if you know that the gene for cystic fibrosis is a certain size, and when this gene is chopped out and applied to the plate it ends up in a specific location on the plate, you can test an individual to see whether they have a clump of molecules at that location. If they do, this suggests they are expressing that gene.
Karyotyping, microarray testing, specific gene testing & DNA sequencing are examples of genetic tests we can do. Describe specific gene testing
Split two strands of DNA. Add a gene probe (single strand of DNA that is complementary to the specific gene you want to test for). When mix DNA with gene probe if gene probe bonds with DNA then you know that particular gene is present.
Karyotyping, microarray testing, specific gene testing & DNA sequencing are examples of genetic tests we can do. Describe DNA sequencing
- Only used for research purposes; no role in clinical practice
- Split two strands of DNA and watch as individual nucleotides are added to a single strand of DNA to reveal exact sequence of nucleotides in DNA
What karyotype do people with Klinefelter syndrome have?
Additional X chromosome(s)
Could be 47XXY, 48XXXY, 49XXXXY….
State some clinical features of Klinefelter syndrome
Note: additional X chromosomes associated with more severe features. Children often appear normal until puberty when may develop:
- Taller height
- Wider hips
- Gynaecomastia
- Weaker muscles
- Lack of secondary sexual characteristics
- Small, firm testicles
- Reduced libido
- Infertility
- Subtle learning difficulties (particularly affecting speech & language)
Discuss the management of Klinefelter syndrome
No cure, treatment centred around helping with features. Involves MDT:
- Testosterone injections
- Advanced IVF techniques to improve fertility
- Breast reduction surgery
- SALT input
- Occupational therapy
- Physiotherapy (strengthen muscles)
- Educational support (for learning disabilities)
Discuss the prognosis of Klinefelter syndrome
- Nearly normal life expectancy
- Slight increased risk of:
- Breast ca compared to other males (
- Osteoporosis
- Diabetes
- Anxiety
- Depression
- Infertility can occasionally be treated with advanced IVF techniques
What would:
- GNRH
- Testosterone
…levels be in Klinefelter syndrome?
- GNRH: high
- Testosterone: low
What is the karyotype for Turner’s syndrome?
- 45XO (only one X chromosome or deletion of the short arm of one of X chromosomes)
State some features of Noonan’s syndrome
- Short stature
- Broad forehead
- Downward sloping eyes with ptosis
- Short stature
- Broad forehead & triangular shaped head
- Downward sloping eyes with ptosis
- Hypertelorism (wide space between the eyes)
- Prominent nasolabial folds
- Low set ears
- Webbed neck
- Widely spaced nipples (wide space between the eyes)
- Prominent nasolabial folds
- Low set ears
- Webbed neck
- Widely spaced nipples
Describe clinical features of Fragile X syndrome
- Delay in speech and language
- Intellectual disability
- Long, narrow face
- High arched palate
- Large ears
- Large testicles after puberty
- Hypermobile joints (particularly in the hands)
- Hypotonia
- Attention deficit hyperactivity disorder (ADHD)
- Autism
- Seizures
- Mitral valve prolpase
State some features of Prader-Willi syndrome
- Constant insatiable hunger that leads to obesity
- Hypotonia in infancy (which can make feeding difficult in infancy)
- Mild-moderate learning disability
- Hypogonadism
- Infertility
- Short stature
- Fairer, soft skin that is prone to bruising
- Dysmorphic features
- Narrow forehead
- Almond shaped eyes
- Strabismus
- Thin upper lip
- Downturned mouth
- Mental health problems, particularly anxiety
State some features of William’s syndrome
- Broad forehead
- Starburst eyes (a star-like pattern on the iris)
- Wide mouth with widely spaced teeth and big smile
- Very sociable trusting personality
- Flattened nasal bridge
- Long philtrum
- Small chin
- Mild learning disability
- Short stature
For Edward’s syndrome, discuss:
- Chromosomal abnormality
- Clinical features
- Prognosis
- Trisomy 18
- Features:
- Micrognathia
- Low set ears
- Rocker bottom feat
- Overlapping fingers
- Clenched fists
- Abnormalities of organs
- Intrauterine growth retardation
- Only a small number of babies born alive with Edward’s syndrome will live past 1yr
For Pierre-Robin syndrome, discuss:
- Features
- Micrognathia
- Posterior displacement of tongue that may result in upper airway obstruction
- Cleft palate
For Cri du chat syndrome, discuss:
- Genetic mutation
- Features
- Chromosome 5p deletion syndrome
- Features:
- Characteristic cry due to larynx & neurological problems
- Feeding difficulties & poor weight gain
- Learning difficulties
- Microcephaly
- Micrognathism
- Hypertelorism
For CHARGE syndrome, discuss:
- Mutation
- Inheritance pattern
- Features
- CHD7 gene mutations
- Autosomal dominant
- Features:
- Coloboma & cranial nerve abnormalities
- Heart defects
- Atresia choanae
- Retardation of growth
- Genital abnormalities
- Ear abnormalities
For Treacher-Collins syndrome, discuss:
- Mutations and modes of inheritance (not asking specifics)
- Features
- Different mutations have different modes of inheritance!
- Features:
- Downward drooping eyes
- Micrognathia
- Very small or absent ears
- Cleft palata
- Coloboma (**a hole in one of the structures of the eye)
