Chromosomes, chromosome abnormalities and birth defects Flashcards
Definition of congenital abnormalities
Abnormalities present at birth that may be due to genetics or infection.
Definition and example of malformation
Primary structural defect - atrial septal defect, cleft lip
Definition and example of disruption
Secondary abnormal structure of organ or tissue - amniotic band wrapping around blood vessel cutting off blood supply to an organ
Definition and example of deformation
Abnormal mechanical force distorting a structure - club foot, hp dislocation
Definition and example of syndrome
Consistent pattern of abnormalities with a specific underlying cause - Down syndrome
Definition and example of sequence
Multiple abnormalities initiated by primary factor - Reduced amniotic fluid leads to Potter’s sequence
Definition and example of dysplasia
Abnormal organisation of cells into tissue - thanatophoric dysplasia
Definition and example of association
Non-random occurrence of abnormalities not explained by syndrome. Cause usually unknown - VATER association
Definition of teratogen
An agent that interferes with normal embryonic or foetal development
Whole-chromosome factors of congenital defects
Numerical - loss or gain of chromosomes
Structural - Translocations, deletions, insertions, inversions
Mosaicism - Normal development of mutated chromosomes alongside normal chromosomes (stage at which mutation occurs affects degree of expression e.g. early mutation = obvious effects)
Effect of age on genetic risk
Increased age of either or both parents results in increased risk of a child with genetic abnormalities
Normal human karyotype
46 chromosomes in somatic cells
23 chromosomes in germ cells
Males have XY as sex-determining pair
Females have XX as sex-determining pair
Process of chromosome banding
Bands labelled according to chromosome number
Short (p) or long (c) arm
Numbered out from centromere.
Used to identify different chromosomes
Nomenclature of karyotyping
- Write total number of chromosomes
- Then a comma
- Then sex chromosomes
e. g. 46,XY or 46,XX
Definition of aneuploidy
An abnormality in the number of chromosomes, caused by the loss or gain of one or more chromosomes
The 3 types of aneuploidy, their definition and whether they can be tolerated or not
Monosomy - loss of one chromosome, nearly always fatal
Trisomy - gain of one chromosome, can be tolerated
Tetrasomy - gain of two chromosomes, can be tolerated
Definition of chromosome translocation
The transfer of genetic material from one chromosome to another when a chromosome break occurs during mitosis or meiosis
The two types of translocation
Balanced
Unbalanced
Features and consequences of balanced translocation
- Even exchange of genetic material between the two chromosomes
- No genetic data lost
- Chromosomes likely to remain the same length
- Little to no physiological effect seen
Features and consequences of unbalanced translocation
- Uneven exchange of genetic material
- Loss or gain of genetic data
- Chromosomes unlikely to remain the same length
- More likely to cause disease
Explain copy number variant/variation
- Phenomenon where sections of the genome are repeated
- Number of repeats in the genome varies between individuals
- Specifically large scale duplication or deletion events that cause variation
Aim of meiosis
To create 4 haploid cells each containing 23 chromosomes
Non-disjunction definition
The failure of the chromosomes to separate correctly in meiosis I or II
Consequences of non-disjunction
- Creates diploid and empty germ cells
- Hence when a diploid and a haploid germ cell combine, a trisomal zygote is created, diploid-diploid = tetrasomal, haploid-empty = monosomal.
The three chromosome aberrations that lead to Down syndrome
- Trisomy 21
- Robertsonian translocation
- Mosaicism
Clinical features of Down syndrome
Newborn period - sever hypotonia, sleepy, excess nuchal skin
Craniofacial - macroglossia, small ears, epicanthic folds, upward sloping palpebral fissures (gaps between upper and lower eyelids)
Limbs - single palmar crease (should be 3, they have 2) wide gap between first and second toes
Cardiac - atrial and ventricular septal defects
General - Short stature, duodenal atresia (abnormal closure/absence of lumen of duodenum)
Low IQ but advanced social skills
Dosage compensation definition
A genetic mechanism in which alleles of a gene automatically regulate the amount of useful product produced such that heterozygous individuals produce the same amount of product as homozygous dominant individuals.
Mechanisms of dosage compensation
- One of each X chromosome in female cells is inactivated. Selection of chromosome to be inactivated is random
- Increased (2x) expression of X chromosome genes in males
- Decreased (0.5x) expression of X chromosome genes in hermaphrodites
Mechanism of sex determination
The SRY gene causes development of testes. Can be translocated to X chromosome in SRY recombination.
Consequences of SRY recombination
SRY gene now on X chromosome
- XX males develop testes but are sterile as other genes on Y chromosome needed for spermatogenesis
- XY females have mutations in SRY gene that lead to sterile phenotypically female individuals
