L37 Introduction to Clinical Genetics 1 Flashcards
(24 cards)
what are fully penetrant conditions?
conditions where genes and environmental factors have no effect eg single gene mutation (mendelian)
what is a low-penetrance condition?
condition where genes have a small influence part, in addition to other genetic and environmental factors, in determining disease susceptibility
what is multiple sclerosis?
a multifactorial condition where genetic factors play a major part in determining susceptibility, but each individual factor has a very low penetrance
how does the impact of genetic disorders have an affect in childhood or in adult life?
in childhood
50% deafness/blindness/severe MR
25% in-patients visits
40-50% deaths
adult life
5% disorders/diseases
10% common cancers
how are genetic disorders classified?
multifactorial single gene chromosomal mitochondrial somatic mutations (cancer)
give examples of how single gene disorders, multifactorial diseases and chromosome disorders may be caused
single gene/ mendelian disorders = mutations in single gene resulting in loss of function
mutlifactorial = variants in genes causing alteration in function
chromosome disorders = chromosomal imbalance causes alteration in gene dosage
what is the difference between multifactorial and chromosomal disorders?
multifactorial - common
“environmental” influences (eg. drugs, infections) + genetic predisposition = susceptibility to a disease
- variants in genes cause alteration of function
- one organ system affected
chromosomal (0.6% liveborn)
thousands of genes may be involved
- chromosomal imbalance causes alteration in gene dosage- multiple organ systems affected at multiple stages in gestation.- usually de novo (trisomies, deletions, duplications)
- in rare cases, can be inherited (translocations)
what are the physical characteristics of down’s syndrome?
round face protruding tongue upslanting palpebral fissures epicanthic folds developmental delay
how is downs syndrome identified on an ultrasound?
short femurs
nuchal translucency - the sonographic appearance of a collection of fluid under the skin behind the fetal neck in the first-trimester of pregnancy
echogenic bowel - an unusually bright appearance of the baby’s bowel on an ultrasound
choroid plexus cyst - cysts that occur within choroid plexus of the brain
sandal gap, single palmar crease - a large gap between the large toe and the first toe or a single crease across the palm (instead of two)
what are microdeletions and give examples of microdeletions
chromosomal anomaly
- chromosomal region is lost: too small to be observed microscopically. identified by use of specific molecular cytogenetic techniques
eg DiGeorge syndrome, williams-beuren syndrome (WBS)
what is DiGeorge Syndrome?
22q11.2 microdeletion
small mouth, prominent nose, congenital heart defects, cardiac abnormality (commonly interrupted aortic arch, truncus arteriosus and tetralogy of Fallot), abnormal facies, thymic aplasia, cleft palate, hypocalcemia/ hypoparathyroidism
what is williams-beuren syndrome (WBS)?
7q11.23 microdeletion (about 26 genes from the long arm of chromosome 7)
bright eyes, stellate irides
wide mouth, upturned nose, long philtrum, flattened nasal bridge, heart defects (heart murmurs, supravalvular aortic stenosis), typical facies; overly sociable (“cocktail party” type personality)
what are the properties of single gene disorders?
- high risks to relatives
- dominant/recessive - pedigree patterns
- some isolated cases due to new dominant mutations
- structural proteins, enzymes, receptors, transcription factors
what is gower’s maneuver?
a medical sign that indicates weakness of the proximal muscles, namely those of the lower limb. The sign describes a patient that has to use their hands and arms to “walk” up their own body from a squatting position due to lack of hip and thigh muscle strength.
seen in duchenne muscular dystrophy
what are the three inheritance patterns?
Autosomal dominant inheritance:
heterozygotes with one copy of the mutated gene are affected
Autosomal recessive inheritance:
homozygotes with two copies of the mutated gene are affected
X-linked inheritance:
males with one copy of the mutated gene on the X-chromosome are affected
what is mitochondrial inheritance?
mitochondrial DNA comes from the mother (unlike nuclear DNA which comes from both parents
what is Leber’s hereditary optic neuropathy?
a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males.
what is the genetic basis of sporadic cancer?
dominantly inherited familial cancer syndromes
both alleles of a gene become inactivated in a particular somatic cell leading to loss of control of growth and unchecked cell proliferation.
what is multifactorial inheritance?
inheritance controlled by many genes with small additive effects (polygenic) plus the effects of the environment
effect of each gene is small
important in population terms
describe pathways of potential therapeutic interest
ONE organ system affected
what is huntington’s disease?
is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition).
Adult-onset Huntington disease, the most common form of this disorder, usually appears in a person’s thirties or forties.
what is familial hypercholesterolemia?
a genetic disorder. It is caused by a defect on chromosome 19. The defect makes the body unable to remove low density lipoprotein cholesterol from the blood.
what is cyctic fibrosis?
a genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections.
what is duchenne muscular dystrophy?
a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact. DMD is one of four conditions known as dystrophinopathies.
what is the difference between penetrance and expressivity?
Penetrance refers to the probability of a gene or trait being expressed. In some cases, despite the presence of a dominant allele, a phenotype may not be present.
Expressivity on the other hand refers to variation in phenotypic expression when an allele is penetrant.
