2: Introduction To Clinical Genetics Flashcards
Chromosomal Disorders (definition)
Problems with number or structure of chromosomes:
Alterations-too many genes, too few genes, altered genes
Polyploidy and Aneuploidy
Insertions, Deletions, Translocations
Single Gene Disorders (definition)
Loss (typical), gain or alteration of the protein
Mendelian inheritance: autosomal (#’d chromosomes) disorders and sex-linked disorders.
Mitochondrial Disorders (definition)
Non-Mendelian Disorders
- Maternal inheritance for mutations in mitochondrial DNA
- Mendelian inheritance for mitochondrial genes on nuclear DNA
Multifactorial Disorders (definition)
Combination of both genes and environment:
- Polygenic: many genes working together
- Teratogenic: mostly environment induced
- Multifactorial: both genetic and environmental
Inheritance Patterns (tools for genetic diagnosis)
Construct Pedigree
Autosomal dominant/recessive, X-linked recessive, X-linked dominant (uncommon)
Autosomal Dominant Pedigree
Father to son is helpful
Equal number of males:females
Does not skip generations
Chromosome Analysis (tools for genetic diagnosis)
Karyotype
FISH
CGH
Exome and Whole Genome Sequencing
Karyotype
Alterations in number, large duplications/deletions, translocations
Down Syndrome
47 (chromosome), XX, +21 (extra chromosome)
Aneuploidy= abnormal number of chromosomes
Dosage is 3
*CAN USE KARYOTYPE
FISH
Detects small deletions (fluorescent in-situ hybridization)
Use probe for area of interest and a control probe
Will see small deletion
Williams Syndrome
Elastin gene on Chromosome 7
Triangular face, small jaw, etc.
*CAN USE FISH OR CGH
Comparative Genomic Hybridization (CGH)
Deletions/Duplications
Can use over whole genome
Take patient (green color) and control (red color) DNA and mix them
Red: deletion
Green: duplication
Yellow: normal
Exome (coding) and Whole Genome Sequencing Problems (tools for genetic diagnosis)
We are all carriers for many diseases
Detect diseases with future consequences
Sequence variation with unknown clinical significance
Biochemical Tests (tools for genetic diagnosis)
Look for abnormal products of metabolism or proteins
- Gas liquid chromatography
- Enzyme assays
- Newborn screening
Phenylketonuria (PKU)
Loss of phenylalanine hydroxylase (PAH) activity
Too much phenylalanine (TOXIC)
Diet: avoid high amounts of protein
DNA Diagnostics (tools for genetic diagnosis)
Direct mutation analysis (DNA sequencing + small DNA probes that hybridize to mutated DNA)
Linkage analysis (not used much anymore)
DNA fingerprinting (variation of sequence analysis to identify individuals: CSI + Paternity)
Non-Mendelian Inheritance (types)
Mosaicism Mitochondrial Inheritance Genetic Imprinting Uniparental disomy (both chromosomes of a pair come from one parent) Unstable triplet repeat mutations
Mosaicism
More than one genotype in a person
Genetic Imprinting
Parent-of-origin difference in gene expression
One of the parental genes is epigenetically silenced
Presymptomatic Testing
Test for genetic mutation that will certainly cause disease later in life
“Family member has one and you want to know”
Looking for fully penetrant genes (have gene and will develop disorder)= definite answer
Ex. muscular dystrophy, CF, Huntington disease, familial adenomatous colon cancer
Offered: to children if medical benefit, to adults but informed consent (affect insurance)
Predisposition Testing
Test for genetic mutation which will possibly cause a disease later in life
“For ladies worried about breast cancer”
Problematic predictions, incompletely penetrant genes
Genetic Counseling Risk
Detection of false paternity
Stigma, including survivor guilt
Loss of employment or insurance
Psychological harm
