Genetic Disorders Flashcards
What are the most common genetic disorders in NZ?
- Familial Cancer (Breast, Bowel)
- Huntington’s Disease
- Muscular Dystrophies
- Chromosomal abnormalities
- Cystic Fibrosis
- Haemochromatosis
Whatare genotype?
The genetic information that is stored in the genetic code
What is DNA?
Deoxyribonucleic acid - a stable macromolecule of the genetic information
What are chromosomes?
Condensed genetic material of an organism located in nucleus
- 22 autosomal pairs, 1 sex pair
What are genes?
Segments of DNA responsible for a particular trait
What are alleles?
Different DNA sequences of the same gene in a population
What does these mean?
- Homozygous
- Heterozygous
- Dominant
- Recessive
- Two same alleles
- Two different alleles
- Expressed always
- Expressed when there are two copies
What are genetic mutations?
Biochemical events leading to accidental errors in duplication, rearrangement, or deletion of parts of the genetic code
What is a point mutation?
Changes of 1 base for another
How can mutations occur?
Inherited (germ) or acquired (somatic)
What are the main types of genetic mutations?
- Single gene (autosomal & sex-linked)
- Alterations in chromosome number
- Alterations in chromosome structure
What are single gene disorders?
Conditions that are caused by a mutation in a single gene in one, or both copies of the gene
- May be present on an autosome or sex-linked chromosome (X)
- Lead to formation of an abnormal protein or decreased
production of a gene product
- Several mutated genes can lead to the same disorder e.g. childhood deafness caused by 16 mutations
What is Marfan syndrome?
- Single gene disorder
- 1 in 20, 000 people
- Mutation on chromosome 15
- Defect in connective tissue affecting various structure (e.g. skeletal, ocular, & cardiovascular)
What are autosomal disorders?
- Caused by mutations in alleles on autosomes
- Most are recessive (need to mutated alleles to be affected)
What is Phenylketonuria?
- A metabolic disorder caused by elevated levels of phenylalanine that are toxic to the brain. Caused by deficiency in phenylalanine hydroxylase (PAH)
- Autosomal recessive disorder
- 1 in 10, 000 people
- Severity of disease rely on amount of deficiency in PAH
- Symptoms develop gradually
- If not treated can cause irreversible brain damage
What are autosomal dominant disorders?
- Mutations needing only 1 mutated allele to cause disorder
- Onset often delayed
- Can occur without affected parent due to new mutations of germ cells
What is Huntington’s disease?
- Degenerative brain disorder
- Causes involuntary movements, nervous system
deterioration, and eventually death - Symptoms include: clumsiness, depression, memory loss, loss of muscle coordination and ability to speak
- Initial symptoms by the age of 40 → People often pass allele on before they know they have it
- Death likely to occur within 12-20 years of onset of symptoms
What is reduced penetrance?
Carrying the mutation but failing to express it
What is variable expressivity?
Mutation which can be expressed differently among individuals
What are X-linked recessive conditions?
- Sex-linked disorders in which an unaffected mother carries one normal and one mutant allele on the X chromosome
- Condition occurs more frequently in males than females
How is the X-linked mutation of red-colour blindness developed?
- It develops from loss or limited function of red or green photopigments (colour-detecting molecules) that are located in cone-shaped cells within the retina
- Is the most common type of hereditary colour blindness
What are atypical single gene disorders?
Mutations not following the Mendelian pattern of inheritance For example: - Triplet repeat mutations - Mutations in mitochondrial genes - Genomic imprinting
What are triple repeat mutations?
Characterised by a long repeating sequence of 3 nucleotides in a gene that disrupts its function
For example:
- Huntington’s disease
- Fragile X syndrome
What are mutations in mitochondrial genes?
- Mutations in the DNA in the mitochondria rather then nucleus DNA
- This DNA has an almost exclusive maternal form of inheritance
- Can affect tissues and organs that are highly dependant on oxidative phosphorylation (e.g., brain, neuromuscular
system)
What are chromosomal disorders?
- Parts of chromosomes are lost or gained or dislocated
- Can result in abnormal gene number or position
- If mutation includes chromosome breakage it may disrupt gene function
- Account for a large proportion of early gestational abortions, congenital malformations, and intellectual disability
What are the chromosomal abnormalities? Structure & number?
1) Alteration in Structure:
- Deletion
- Duplication
- Inversion
- Ring
- Translocation
2) Alteration in Number
- Monosomy
- Trisomy
- Tetrasomy
- Triploidy
What is deletion?
Simple loss of a chromosomal segment
What is duplication?
The presence of two copies of a chromosomal region
What is inversion?
A segment of a chromosome breaks off and then reattaches in the reversed direction
What is a ring chromosome?
Breakage and two ends joining to form ring
What is Cri Du Chat?
- Genetic disease caused by a heterozygous deletion of the tip of the short arm of chromosome 5
- 1 in 50, 000 people
Characteristics: - Moon like face
- Often mentally challenged
- Distinctive catlike mewing cries as infant
- Abnormal voice box development
- GI and cardiac complications
What are chromosomal duplications?
- Extra copy of a chromosome region consisting of an extra chromosomal arm or part of an arm
- Hard to detect and are rare
- Duplications supply additional genetic material capable of evolving new functions
What is first division nondisjunction?
Failure of the two chromosomes to separate into one in the first meiotic division
What is second division nondisjunction?
Failure of the chromosome to separate into halves in the second meiotic division
How does down syndrome occur and what is it?
- Trisomy of chromosome 21
- 95% caused by nondisjunction
- Increased risk with increased maternal
- Usually apparent at birth
- Causes a combination of birth defects including intellectual disability and characteristic facial features
What is turner syndrome
- Absence of all or part of one of the female’s X chromosome
- 1 n 5, 000 people
- 99% of foetuses spontaneously aborted in 1st trimester
- Diagnosis is often delayed until late childhood/early adolescence
- Early diagnosis is important for ongoing assessment and treatment (Growth hormone, Oestrogen therapy for secondary sexual
characteristics) - Women with Turner syndrome have increased morbidity due to cardiovascular disease and gastrointestinal, renal, and endocrine disorders
What are multifactorial disorders?
- Usually several genes are involved and no clear pattern of inheritance within a family
- Often environmental contribution
- Difficult to predict
- Risks of recurrence are somewhat increased for close relatives of an affected individual and with severity of disorder
When can multifactorial disorders be expressed and what are some examples?
- Foetal life and be present at birth (congenital) e.g. Cleft lip or palate, clubfoot, congenital heart disease
- Later in life (environmental contribution is likely greater) e.g Alzheimer’s, psychiatric disorders, diabetes, obesity, cancer
What are teratogens?
- Environmental agent that produces abnormalities during embryonic or foetal development
Can act via:
1) Direct exposure of the pregnant women, foetus or embryo
2) Exposure to an agent with a slow clearance rate prior to pregnancy
3) Exposure to a teratogenic agent that caused damage to reproductive cells prior to pregnancy - Teratogenic agents include: radiation, environmental chemicals and drugs, infectious agents
What is organogenesis?
- Time interval of differentiation and organ development
- In humans from day 15 to day 60 after conception
- Insult during the first 2 weeks after fertilisation may interfere
with implantation causing abortion or early resorption
What is epigenetic’s?
- Changes in gene expression without changes in gene sequence
- Regulate activation and repression of genes
- Flexible mechanisms (Occur during development as stem cells, also in response to environmental signals)
- Two main kinds of epigenetic information
1) Methylation (e.g., genetic imprinting)
2) Histone modifications
How do epigenetic’s work?
- DNA remains the same but histone modifies what markers are genes are transcribed into RNA
- E.g. neuronal cell will express genes to enable to develop axon and dendrites but this will be suppressed in same genes in liver cell
What are prenatal tests for screening?
- Give an estimate of the chance a disorder will occur
- Identify women < 35 years old with higher risk
pregnancies who can be offered diagnostic testing - Less invasive than diagnostic testing
- Not a “Yes” or “No” answer
- False +, False -
What is a maternal serum screen?
- Maternal blood test measures the level of specific proteins produced by the foetus & placenta
- Maternal age + protein levels are combined to produce an estimated risk for chromosome abnormalities and neural tube defects
- Not applicable for all pregnancies
What is a prenatal ultrasound?
- Used for screening (and diagnostic)
- Non-invasive
- Higher detection rate when combined with other screening methods (e.g., blood tests)
What is Nuchal translucency?
- Measurement of the thickness of the fluid that accumulates under the skin at the back of the neck
- Helps with detecting Down syndrome
What are prenatal diagnostic tests?
- Give a clear answer (usually) about whether or not the foetus has a particular condition
- Provide the most accurate results
- Involve invasive procedures which carry a risk of
miscarriage - Are only routinely offered to those at higher risk
What is amniocentesis?
- Karyotype from a sample of amniotic fluid
- Identifies major chromosome anomalies
- Does not identify gene mutations, very small chromosome changes, or structure and development of the foetus
- Performed after 14 weeks gestation
- Risk of miscarriage 1/200
- Accuracy ~99.5%
What is chorionic villis sampling (CVS)?
- Karyotype analysis from a sample of the placenta
- Identifies major chromosome anomalies
- Does not identify gene mutations, very small chromosome changes, or structure and development of the foetus
- Performed 10-12 weeks of gestation
- Risk of miscarriage 1/100
- Accuracy ~96%
