Chromosomes, chromosome abnormalities and birth defects Flashcards
Congenital defects; Age effects; Chromosomes and chromosome abnormalities;Meiosis; Down syndrome; Dosage compensation
How are congenital defects classified?
Single -Malformation -Disruption -Deformation -Dysplasia Multiple -Sequence -Syndrome -Association
Define and give an example of malformation
Primary structural defect
Single organ showing multifactorial inheritance
e.g. cleft lip
Define and give an example of disruption
Secondary structural defect of organ/tissue Caused by ischaemia NOT genetic Extrinsic factor affects development e.g. amniotic band = digital amputation
Define and give an example of deformation
Abnormal mechanical force distorts structure
Happens later in pregnancy - organ works but has deformities
e.g. club foot
Define and give and example of dysplasia
Abnormal organisation of cells within tissues
e.g. thanatophoric dysplasia
Define and give an example of a sequence defect
Multiple abnormalities initiated by a primary factor
Can be genetic
e.g. Potters sequence
Define and give an example of a syndrome
Consistent pattern of abnormalities with specific underlying cause
e.g. Downs syndrome
Define and give an example of an association defect
Non random occurrence of abnormalities
Not explained by a syndrome
Unknown cause
e.g. VATER association
How do non-genetic factors lead to congenital defects?
Problems with chromosomes
- numerical - aneuploidy
- structural
- mosaicism
What are the 5 different types of structural problems that can occur with chromosomes?
Translocations Deletions Insertions Inversions Rings
Define aneuploidy and its 4 main types
Loss or gain of one or more chromosomes
Monosomy - loss of 1, almost always lethal
Disomy - normal
Trisomy - gain of 1, can be tolerated by specific chromosomes
Tetrasomy - gain of 2, can be tolerated for specific chromosomes
Define mosaicism
Where different cells in the same individual have different numbers or arrangements of chromosomes
What does a normal human karyotype show?
46 chromosomes
22 autosomal pairs, 1 sex pair
XY males XX females
Define chromosome translocation and its possible biological effects
Exchange of material between two non-homologous chromosomes
May be normal phenotype if same genes, just rearranged
Can cause gene disruption if translocation from middle or is a fusion product
Affects reproduction
Define Robertsonian translocation
P lost, Q parts join on acrocentric chromosomes
occur with 13,14,15,21,22
What 3 different chromosome aberrations lead to Down’s syndrome?
Trisomy 21 - non-disjunction of homologous chromosomes in meiosis 1
Robertsonian translocation - full copy of 21 attaches to a different chromosome, usually 14
Mosaicism - v rare, mix of cells with normal chromosomes and some with 47 chromosomes
What are the main clinical features of Down’s syndrome?
During newborn period - hypotonia, lethargy, excess nuchal skin
Craniofacial features - macroglossia, small ears, epicanthal folds, sloping palpebral features, brushfield spots
Limbs - single palmar crease, wide gap in 1st and 2nd toes
Cardiac - septal defects, atrioventricular canal
Other - short stature, duodenal atresia
Low IQ but advanced social skills
How does parental age affect genetic risks?
Increased maternal age has strong association with higher incidence of Down’s syndrome at birth
Define non-disjunction
Failure of homologous or sister chromatids to separate properly during cell division
Define copy number variant
Variation in the number of repeats of sections of the genome in the genome `
Define dosage compensation
Process by which organisms equalise expression of genes between members of different biological sexes
What are the 3 mechanisms of dosage compensation?
Random X inactivation in females
Increased X expression in males
Decreased X expression of both X chromosome genes in hermaphrodites
Why is sex determination not solely based on sex chromosome karyotype?
SRY gene (testes development) can translocate to X chromosome in SRY recombination
Develop testes but are sterile because no Y so no spermatogenesis
XY females are infertile
What is monosomy X and what does it cause?
Turner’s syndrome
Loss of X or Y in PATERNAL meiosis
What are the clinical features of Turner’s syndrome?
Generalised oedema Neck swelling Webbed neck Low set ears Low hairline Short stature Diabetes and other problems
What is Kleinfelter’s syndrome and what causes it?
non-dysjunction XXY
Phenotypically male
Tall with learning difficulities
