Gen Flashcards
What are the single congenital defects
Malformation
disruption
Deformation
dysplasia
What are the multiple congenital defects
Sequence
syndrome
Association
Define malformation
Primary structural defect
As a result of intrinsically abnormal development
Define disruption
Defect as a result of extrinsic interference with originally normal development
Define Deformation
Mechanical force is causing abnormal shape, form or position
Distorting structure
Define dysplasia
Abnormal organisation of cells in a tissue
Define sequence
Pattern of multiple abnormalities
Derived single known prior anomaly or factor
Define syndrome
Multiple abnormalities
Pathogenically related
Specific underlying cause
Eg. Downs
Define Association
Non-random occurrence of abnormality
not explained by syndrome due to unknown cause
What are the three problems that can occur with chromosomes
Aneuploidy- loss or gain of chromosomes
Structural- translocations, deletions, insertions, inversions, rings
Mosaicism- different cell lineages
Transfer of genetic material from one chromosome to another is normal in balanced translocations unless…
Disruption of a gene
Fusion product
Define monosomy
Loss of a single chromosome almost always lethal
Define trisomy
Gain of one chromosome can be tolerated for specific chromosomes
Define Mosaicism
Where different cells in the same individual have different numbers or arrangements of chromosomes
What type of trisomy is the most common
Trisomy 16
Fatal in Utero -miscarriage
What types of trisomies can be viable
13, 18, 21
13- patau syndrome
Heart defects, mental retardation
18- Edwards syndrome
Heart defects, kidney malformation, digestive tract defects, mental retardation
What are the clinical features of down syndrome
Newborn period
Hypotonia, lethargic, eXcesS nuchal skin
Craniofacial
Macroglossia, small ears, sloping palpebral fissures
Limbs
Single Palmar crease, wide gap between first and second toes
Other
Short stature, douodenal atresia
Low IQ but advanced social skills
What are the three different chromosome aberrations which lead to downs
Trisomy 21
90% due extra chromosome from mum
Non-disjunction homologous chromosomes in meiosis 1 (3 copies instead of 2)
Translocation
Break In Acrocentric chromosomes (13,14,15,21,22) and fusion long arms
No. Chroms still 46 but part/full copy chrom 21 attaches another chrom
Mosaicism
Mix of two types of cells some containing 46 chromosomes some containing 47
What is Monosomy X
Turner’s syndrome
Loss of X or Y in paternal meiosis
(Other causes: ring chromosome, single arm deletion, Mosaicism)
What are the characteristics of Turner’s
Prenatal
Generalised oedema and neck swelling
Newborn/child
Odematous hands and feet, Webbed neck, low set ears, low posterior hairline, broad chest, aortic defects, urinary defects
Adult
Short stature, infertility, diabetes, hypothyroidism
Normal intelligence
What is XXY
Klinefelter’s syndrome
Phenotypically male
Learning disability
Tall and infertile
Define dosage compensation
Process by which organisms equalise expression of genes between members of different biological sexes
What are the two mechanisms of dosage compensation
- Random in activation of single X-chromosome in females
2. Increased (2x) expression of X-chromosome genes in males
Explain why sex determination is not solely based on sex chromosome karyotype and how it is possible to be chromosomally one gender and phenotypically opposite
SRY gene - testes development
This gene can be translated to X-chromosome in SRY recombination
XX males develop testes but are sterile because other Y-chromosome genes important in spermatogenesis
XY females infertile
What are the characteristics of a monogenic disorder
List examples
Clear inheritance
no environment
individually rare
Eg. Huntington’s cystic fibrosis and haemophilia
What are the characteristics of a complex disorder
List examples
No clear inheritance
Environment essential
Common
Eg. Type II diabetes, schizophrenia
Define polymorphism
Mutation at >1%freq. in given population
Why are pedigree diagrams important
Identify genetic disease running in family Identify inheritance patterns Aid diagnosis Assist in management of condition Identify relatives at risk of disease
Difference btwn autosomal recessive and autosomal dominant
At least one parent affected in autosomal dominant whereas no affected parent in autosomal recessive
Example of autosomal dominant disease
Huntington’s disease Cell death in Basal ganglia Unstable CAG triplet repeats 10-35 unaffected 27-35 unaffected, risk affected kid 35-40 sometimes affected 40+ affected
What is example of an autosomal recessive disease
Cystic fibrosis
Mutation CFTR gene chrom 7
Coding chloride channel
What is special about X-linked recessive diseases
No affected parents
Transmitted by carrier female
Only male affected
Example of an ex-linked recessive disease
Haemophilia
Blood clotting disorder causing easy bruising and heavy bleeding
A and B (rarer) types
Haemophilia A -F8
Haemophilia B -F9
Both genes are on the X-chromosome
What are the three types of genetic heterogeneity
Same gene, different mutations leading to different symptoms
Same disease, different genes
Same disease, different genes, different inheritance patterns
Define incomplete penetrance
Symptoms are not always present in an individual with a disease causing mutation
Define variable expressivity
Disease severity may vary between individuals with the same disease causing mutation
Define phenocopy
Having the same disease but with a different underlying cause
Explain mechanisms of dominant conditions
Mutations leading to toxic protein effects of mutated gene which mask normal copy
Explain mechanisms of recessive conditions
Mutations cause an absence of a functional protein so the normal copy is absent
How can you treat dominant conditions
Neutralise the toxic protein effects or switch off the mutant gene
What is Genomic imprinting
You inherit two copies of genes
one from mother one father usually both copies of the each gene active but sometimes one copy is turned on
which copy is made active depends on parent of origin some genes and only active only when inherited from father etc.
What is uniparental disomy
A person receives two copies of chromosome or part of a chromosome from one parent and no copies from the other parent
Two examples of uniparental dysomy
Prader Willi syndrome and Angelman syndrome
What are the symptoms of Prada Willi syndrome
Due loss Paternal chr15
Hyperphagia leading to obesity Mental impairment Behavioural problems Muscle hypotonia Short stature small hands and feet Delayed or incomplete puberty Infertility
What are the symptoms of Angelman syndrome
Due loss maternal chr15
Developmental delay and speech impairment
Movement disorder
Behavioural uniqueness e.g. happy demeanours, excitable, short attention span
Seizures
List examples of mitochondrial disorders
MELAS
LHON
Describe symptoms LHON
More common in males
Degeneration of retinal ganglion cells
Loss of central vision
Most become blind
Describe symptoms MELAS
Progressive and ultimately fatal
Muscle weakness vomiting headache dementia
Single mutation in several genes
List two examples of inborn errors of metabolism currently included in UK national neonatal screening programs
Phenylketonuria PKU
MCADD DEFICIENCY
Describe what PKU is
Inborn errors of metabolism and included in the UK national neonatal screening programs
Blonde hair/blue eyes no melanin
eczema and must Odour
Describe what MCADD Deficiency is
Inborn errors of metabolism and currently included in UK national neonatalscreening program
Most common disorder of fatty acid oxidation
Medium chain acyl CoA dehydrogenase
Treatment of PKU
Remove Phenylalanine from diet
Protein supplements to supply other AAs
Strict diet in preg
Early detection
Treatment of MCADD deficiency
Avoid fasting
Nutritional supplements at times of increased stress
What is the difference between somatic and germline mutations
Somatic occurs in body cells and cannot be passed on to offspring
Germline mutations in gametes which can be passed on to offspring
What is the difference between driver and passenger mutations
Passengers are mutations that don’t contribute to the development of cancer but have occurred during growth cancer
Drivers contribute to cancer development
What are oncogenes
Promotes growth and proliferation in cells
Signal in cascades and mitogenic pathway activation
E.g..growth factors, transcription factors, tyrosine kinases
What are tumour suppressor is
Regulate cell division, DNA damage checkpoints, Apple ptosis, DNA repair
