Principles of genetic inheritance Flashcards
Describe the process of mitochondrial inheritance
*Disruption of the mitochondrial functions leads to reduced energy form of ATP and accumulation of reactive oxidase species which are damaging to the cell and activation of cell death through apoptosis. At cell division, mitochondrial are distributed unequally and do not necessarily reflect the ratio found in the progenitor cell. When the level of mutant mitochondria exceeds a certain threshold, cell express dysfunction
Explain the terms homoplasmy and heteroplasmy
HOMOPLASMY IS A TERM USED IN GENETICS TO DESCRIBE A CELL WHOES COPIES OF MITOCHONDRIAL DNA ARE ALL THE SAME WHEREAS HERTEROPLASMY IS THE PRESENCE OF MORE THAN ONE TYPE OF MITOCHONDRIAL DNA WITHIN A CELL OR INDIVIDUAL . THIS IMPLIES THAT SOME OF THE mDNA IS NORMAL(WILD TYPE) AND SOME MITOCHONDRIAL DNA CONTAINS A MUTATION
Briefly describe some clinical phenotypes associated with mitochondrial dysfunction
- Muscle symptoms: Ptosis, external ophthalmoplegia, muscle pain, progressive proximal muscle weakness, fatigue, cardiomyopathy
- CNS symptoms: Ataxia, seizures, stroke, early onset of dementia, and deafness
- Metabolic disorders: Diabetes mellitus, liver dysfunction
Criteria to use in order to diagnose a mitochondrial dysfunction?
- A common condition occurs with atypical features eg stroke in a 3-year-old
- More than 3 organ systems are involved in progressive disorders eg muscle weakness, ophthalmoplegia, and arrhythmias
- MELAS: Mitochondrial encephalomyopathy, lactic acidosis,stroke-like episodes
- NARP: Neurogenic weakness with ataxia and retinitis pigmentosa
Explain the concept of genetic imprinting
*Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed in a parent -of -origin-specific manner
how does genetic imprinting impacts the expression of genetic diseases
About 150 ( of our 2000) genes are imprinted, this means that they have different expressions (active/silent) depending on whether they are derived from a sperm cell or egg cell.
how does genetic imprinting impacts the expression of genetic diseases
About 150 ( of our 2000) genes are imprinted, this means that they have different expressions (active/silent) depending on whether they are derived from a sperm cell or egg cell. If an individual for some reason has 2 paternally or maternally expressed genes or only a single copy of a gene,a disease may be apparent
Give an example of genetic imprinting
Gene H19(suppress growth) is expressed on the maternal allele and gene IGF2(stimulate growth) is expressed from the paternal allele. For a person to have a normal function, expression of H19 is necessary for normal growth)
Clinical manifestation of genomic imprinting dysfunction
1.Beckwith - Wiedemann syndrome
Cause: Overexpression of IGF2 gene
Phenotypes : Large birth weight Tall stature in childhood Macroglossia Omphalocele / umbilical hernia Risk to develop embryonal tumors
- Russell Silver syndrome
Cause: Overexpression of H19 gene
Phenotypes : small for gestational age Very short stature small chin with triangular-shaped face feeding difficulties
What is uniparental disomy
Uniparental disomy refers to the situation in which 2 copies of a chromosome come from the same parent instead of 1 copy coming from the mother and 1 copy coming from the father
Define triplet repeat
A tri-nucleotide repeat expansion is the DNA mutation responsible for causing any type of disorder categorized as a tri-nucleotide repeat disorder
How abnormalities of triplets expansion cause disease
*Normal repeat size: The number of tri-nucleotide repeats that normally occur in the sequence of a gene, resulting in s functional gene product
> Pre-allele: The number of tri-nucleotide repeats is higher than the normal range but will not cause disease in the person with the pre-mutation allele
> Intergenerational expansion: A pre-mutation allele is regarded as unstable during meiosis with the possibility of the expansion increasing/decreasing in size in the cell progeny ie there is a risk for an affected child
Disease range allele: The number of tri-nucleotide repeats is much higher in the normal range and affects the production of normal protein from the gene ; a disease state is likely to develop
General characteristics of triplet repeat disorder
- Age of onset varies
- Severity varies ,it is dependent on triplet repeat size
- May display early onset and increased severity in successive generations ,in triplet size increase.
example / triplet repeat / form of inheritance >Fragile X /CGG/XL >Myotonic dystrophy /CTG/AD >HD /CAC/AD >Friedreich's ataxia /GAA/AR
Discuss the clinical manifestations of Fragile X syndrome expressed by affected males and females
Both males and females can be affected by clinical features including intellectual problems, language delay, and behavioral problems.
1. Affected males > Variable developmental delay ( mostly moderate MR-IQ 35-50) >Language delay : *Poor / no speech *Burst of repetitive speech
> Behaviour
- Hyperactivity
- poor eye contact
> Physical features
- large ears, long face, macrocephaly
- Prominent mandible
- post-pubertal macro-orchidism (large testicles )
- Ligament laxity(hyper-extendiable joints ) ,mitral valve prolapse ,hypotonia ,epilepsy ,hypertention ,GORD ,strabismus ,recurrent media
- Affected females
* full mutation (.200 repeats )
* less severe mental retardation than affected males
* Behavioral problems
Discuss the Fragile X syndrome care and prevention?
>Genetic counseling and psychosocial support > Schooling: Remedial education and vocational training (individual attention, small class size and avoid sudden change
> Interventions
- Speech, occupational, and physiotherapy
- Treatment ADHD
- Ensure hearing and vision are normal
- Routine management of hypertension, mitral valve prolapse, seizes and GORD
> Social assistance
- Social grants
- Address issues of placement, discrimination, and abuse
