clinical genetics Flashcards
what are multifactorial genetic disorders?
disorders affecred by environmental and genetic factors
one organ system affected
what are single gene genetic disorders?
mutation in a single gene which affect protein in the body
dominant/recessive patterns
what are chromosomal genetic disorders?
thousands of genes involved
multiple organ systems affected
trisomes, deletions and duplications - translocations are inherited
what are mitochondrial genetic disordes?
genetic disorders in the mitochondria - inherited from the mother
what are somatic genetic disorders?
cancer
what is penetrance?
the frequency with which the characteristic controlled by a gene is seen in individuals possessing it
what is expressivity?
differing clinical features/ phenotype among those with the same alleles/ genotype
give an example of a mitchondrial disorder
leber hereditary optic neuropathy
when does crossing over occur?
meiosis II
what is the structure of a chromosome?
long continuous piece of DNA with genes in linear order
chromosomes also contain RNA, histone protiens and non-histone proteins as packaging
during metaphase, chromosomes become highly condensed
how do chromosome abnormalities cause issues?
they alter the amount of products of genes invovled
what are numerical chromosome abnormalities?
change in number of chromosomes
aneuploidy - different number of a particular chromosome in a cell - monosomy, trisomy
polyploidy - having more that 2 paired sets of chromosomes - triploidy
what are structural chromsome abnormailites?
translocations - reciprocal (exchange between 2 chromsomes) or robertsonian (part of chromsome on another)
deletions
duplications
inversions
what are different cell line chromosome abnormalities
2 or more genetically different cells in the body
what are most chromosome abnormalities caused by?
de novo events in meiosis
why do new mutations increase with paternal age?
due to greater number of germ cell divisions
what is mosaicism?
after fertilisation embryo undergoes abnormal separation of chromsomes in one of its cells in mitosis = mitotic non-disjunction
results in fetus with 2 or more populations of cells.
give an example of mosaicism?`
down syndrome
2 population of cells - 45XY-21 and 47XY+21
What is gametogenesis?
process by which cells undergo meiosis to form gametes
what is non-disjunction?
failure of homologous chromosomes to separate properly during cell division
what is centric fusion/robertsonian
breakage of 2 acrocentric chromosomes at or close to centromeres with subsiquent fusion
what are the symptoms of down syndrome?
clinical features: round face protruding tongue upslanting palpebral fissures epicanthic folds developmental delay
what is the cause of down syndrom?
trisomy 21 karyotype
what is karyoping?
determination of the karyotype to detect chromosomal abnormalities
what is the normal chromosomal karyotype?
46,XY or 46,XX
What is flourescence in situ hybridization? (FISH)
production of FISH probes for olfactory homolgues with flourescent markers
apply to chromsome that has been denatured and floursecence occurs at ;points
what is FISH used for?
to detect specific DNA sequecnes in interphase nuclei or chromsomes - such as willams-beuren syndrome
name 3 autosomal trisomies
down sydrome
edwards syndrome
patau syndrome
what is edwards syndrome?
autosomal trisomy 18
multiple malformations - of heart and kidney inparticular
clenched hands with overlapping fingers
what is patau syndrome?
trisomy 13
multiple malformations
affects midline structures - incomplete lobation of the brain, cleft lip, congenital heart disease
what are anomalies of sex chromosome number caused by?
abnormal gametes with unusual complements of sex chromsomes
what is the karyotype of kinefelter syndrome and its symptoms?
47,XXY infertility poorly developed sexual characteristics gynaecomastia (males get boobs) and osteoporosis (weak bones) tall
what is the karyotype and symptoms of turner syndrom?
45,X
short stature, wide carrying angle of arms
primary amenorrhoea
congenital heart disease
what are microdeletions?
chromosomal regions that are lost , too small to be observed microscopically, identified by use of specific moleuclar cytogenetic techniques
2 example sof microdeletions?
DiGeorge syndrome
williams-beuren syndrome
what are the typical facial features of DiGeorge syndrome?
small muth, prominant nose
what are the typical facial feature sof williams-beuren syndrome?
bright eyes, wide mouth, upturned nose, long philtrum, flattened nasal bridge
overly sociable
give 4 examples of single gene disorders
huntingtons disease
familial hypercholesterolaemia
cystic fibrosis
duchenes muscular dystrophy
what are some symptoms of huntigntons disease
irritability depression involuntary movements poor coordination trouble learning new infromation trouble making decisions
what is the cause of huntingtons disease?
altered HTT gene - the CAG repeat increases in size
what is familial cholesterolaemia?
disorder if cholesterol metabolism
causing premature atherosclerosis and cardiovascualr disease
autosomal dominant mutation in LDLR - encodes LDL cholesterol receptor
signs of familial cholesterolaemia?
high LDL
cholesterol deposits such as arcus cornealis
what is cystic fibrosis?
autosomal recessive condition of defective CF gene
affects secretory glands including mucus and sweat glands
what is duchenne muscular dystrophy
mutation in DMD gene which produces dystrophin
absence of dystrophin cuases disorganisation of muscle and invasion by fibrous tissue
=weak proximal muscles
