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Pedigree• Visual representation of family tree with history
of studied trait– Proband – person originally studied
• Oldest generation at the top; youngest generation at the bottom– Roman numerals used for generations (I being the
oldest)
• Numbered from left to right within a single generation
Autosomal recessive traits
• Trait seen in roughly equal amounts of males and females
• Seem to skip generations– Affected individual can
have unaffected parents
Autosomal dominant
• Equal frequency of males and females
• No skipping of generations
• All affected individuals have an affected parent
• (affected individuals tend to be heterozygous)– Some traits are lethal in
homozygous form• Achondroplasia
X linked recessive
• Affected phenotype seen more commonly in males
• Tend to skip generations
• Affected males do not pass trait to sons
X linked dominant• Do not skip generations
• Seen in both males and females
• Females may be more numerous – Females can get disease
from either parent while males can only get from mother
• Affected male will have 100% daughters affected
Y linked
• Only males affected
• Affected males will have 100% affected sons
• Do not skip generations
Twin studies
• Dizygotic – Non-identical twins; fraternal – 2 separate eggs fertilized– 50% average relatedness; same as any sibling
pair
• Monozygotic– Identical – One zygote that splits very early in embryonic
development
Concordance studies• % of twin pairs that have the same trait
• Monozygotic twins are 100% genetically identical; dizygotic approx 50%
• Used to evaluate genetic vs environmental factors
• Genetic influenced traits will show higher concordance in monozygotic twins
Adoption studies• Examines effects of genes (biological
parental traits) vs environment (adoptive parental traits)
• Adoption parents have 0% relatedness to adopted child, but share same environment
• Adoptees tend to resemble biological parents (obesity, alcoholism)
Genetic counseling• Provide education regarding genetic diseases –
risks, testing options– Provides NON-DIRECTIONAL information– Informed consent
• Reasons for seeing a genetic counselor– Positive family history– Advanced maternal age– Abnormal prenatal test results– Infertility– Ethnic background
Prenatal testing • Ultrasound
– Can be performed as early as several weeks after fertilization
– Noninvasive
– Gives image of fetus• Anatomical
abnormalities, neural tube defects, nuchal translucency, amount of amniotic fluid, fetal size
Prenatal testing • Amniocentesis
– 15-18 weeks
– Trans-abdominally or trans-vaginally, depending on placental location
– Ultrasound guided
– Needle inserted and ~15ml of fluid extracted
• Fluid can be tested directly (biochemical) or fetal cells cultured prior to testing (biochemical, molecular, cytogenetics)
• Each ml of fluid contains only ~10-15 cells
Prenatal testing• Chorionic villi sampling
(CVS)– Ultrasound guided
– Small section of chorion is suctioned off (10-15mg)
– Large number of fetal cells reduces time/need for culturing
– Increased risk for limb reduction of performed at earlier gestation
• Eliminates proper blood supply to developing limb
Prenatal testing• Fetal cell sorting – in development
– Isolation of fetal cells from maternal bloodstream
– Minimally invasive
• Pre-implantation – IVF procedure– One cell is removed from 8-16 cell embryo
and tested• Only “healthy” embryos are implanted
Postnatal testing
• Newborn screening – Panel varies from state to state
• Heterozygote/carrier testing– Positive family history or particular ethnic
background– Biochemical or molecular testing
• Depends on specific disease involved
Postnatal testing
• Pre-symptomatic testing– Inherited cancer alleles – increased risk for cancer– Late-onset diseases
• Huntington disease
• Chromosome analysis/cytogenetic testing– Diagnostic and prognostic value in cancer– Infertility – Child with structural chromosomal abnormality
• Inherited or de novo mutation
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