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MG2 Medical Genetics
Acronyms
Toronto Notes 2019
Acronyms
CF
CNV copy number variation
FISH fluorescence in situ hybridization FTS first trimester screening
cystic fibrosis
NIPT Non Invasive Prenatal Testing ONTD open neural tube defect
PKU phenylketonuria
SCID severe combined immunodeficiency US ultrasound
GA IPS
Terms
• Penetrance:extentthatageneisobservablyexpressedinanindividualthatcarriesit
• Expressivity:extentofgeneexpression
• Geneticheterogeneity:geneticdisordercanarisefromdifferentallele/locusmutations
• Phenotypicheterogeneity:mutationsinthesamegeneresultinginmultiplediverseclinical
manifestations and degrees of severity
• Uniparentaldisomy:twofullorpartialcopiesofachromosomefromoneparentandnochromosome
from the other parent
Mendelian Inheritance
disorders caused by mutation of one or both copies (alleles) of a gene, inherited in one of three patterns • autosomal:whendisorderiscausedbymutationsingenesononeof22pairsofautosomes
(chromosomes 1-22)
■ autosomal dominant: one copy of a gene with a mutation is enough to cause a disorder
■ autosomal recessive: both copies of a gene must have mutations to cause a disorder; one copy of
mutation = carrier
• X-linked: when disease is caused by mutations in a gene on the X chromosome
Triplet Repeat Expansions
• disorderinwhichtrinucleotiderepeatsincertaingenesexceedthenormalnumberandresultinaltered gene expression or production of an abnormal protein (e.g. Fragile X syndrome, Huntington disease)
■ these disorders can demonstrate genetic anticipation, where there is an amplification of trinucleotide repeats with an increase in disease severity across generations
■ length of segment is proportional to severity of clinical phenotype
Imprinting Disorders
• imprintedgenesareexpressedentirelyfromeitherthematernalorpaternalallele,dependingonthe gene (parent-of-origin gene expression)
• occurwhenamutationdisruptsthenormallyexpressedalleleofimprintedgene(e.g.Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome) or through uniparental disomy of the normally silenced allele
Mitochondrial Disorders
• disorderscausedbymutationsoftheDNApresentinmitochondriaornucleargeneswhoseprotein products are important for mitochondrial function
• inheritancepatternofmitochondrialDNAmutations:motherpassesonthedefecttoallherchildren; father cannot pass on defect since embryo only receives mitochondria from the mother (in the egg)
Copy Number Variation
• differenceintheamountofgeneticmaterial
■ decrease: deletion of a chromosomal region, leaving only one copy of the genetic material in that
region (e.g. 22q11.2 deletion syndrome due to deletion on chromosome 22)
■ increase: duplication of a chromosomal region, resulting in more than two copies of the genetic
material in that region (e.g. Potocki-Lupski syndrome due to duplication of chromosome 17p11.2)
or more than one copy in the case of X chromosome material in a male • CNVscanbepartofnormalspectrumofgeneticvariation
Gestational Age
integrated prenatal screening
Introduction to Genetics
Background