1. Chapter 6 – Pedigree Analysis and Applications

2. 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

6. Autosomal recessive traits
Trait seen in roughly equal amounts of males and females
Seem to skip generations
Affected individual can have unaffected parents

7. 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

8. X linked recessive Affected phenotype seen more commonly in males
Tend to skip generations
Affected males do not pass trait to sons

9. 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

10. Y linked Only males affected
Affected males will have 100% affected sons
Do not skip generations

11. Twin studies Dizygotic Monozygotic 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

12. 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

14. 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)

16. 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

17. 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

18. 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

19. 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

20. Prenatal testing Fetal cell sorting – in development Pre-implantation
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

21. Postnatal testing Newborn screening Heterozygote/carrier testing
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

22. 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