Pedigrees and Genetic Tests

Ch. 6

Pedigree tip

Individuals entering a pedigree laterally are often normal homozygous, but not always

Autosomal Recessive Pedigree

• Males and females even

• Skips generations

• More common when parents are related

• Parents must be heterozygous

Consanguinity (inbreeding)

• Closely related individuals marry/reproduce (shown on pedigree with a double line)

  • Increases homozygosity → exposes recessive alleles

• Common in Royal Families

Autosomal Dominant pedigree

• Males and females even

• Present in each generation across a pedigree, but it can be lost within a lineage.

  • Once lost, it will not reappear

X-Linked Recessive Pedigree

• More males affected

• Traits skip a generation

• Sons of affected fathers are unaffected

• Daughters of affected fathers are carriers

• Affected mothers must pass it on to their sons

X-Linked Recessive Example

• Hemophilia: bleeding disorder

• European royal families married closely and there were carriers of the disease and members who had it

X-Linked Dominant Pedigree

• Slightly more females

• Each generation

• Sons of affected fathers are unaffected

• Daughters of affected fathers are affected

Y-Linked Pedigree

• Males only

• Affected fathers have affected sons

• Each generation

Useful Tips for Pedigrees:

• Does the trait skip generations? If yes, it’s probably recessive

• Do affected males pass the trait on to their sons? If yes, it can’t be X-linked

• Are more males than females affected? If yes, it’s probably X-linked

Twins: Monozygotic

• Identical twins - single egg

• Due to chance

Twins: Dizygotic

• Nonidentical or fraternal twins - two separate eggs

• Can “run” in a family

Concordance in Twins

• Dizygotic twins = same environment, 50% same genetics

• Monozygotic twins = same environment, 100% same genetics

• Both twins develop a trait: they are concordant

• Only one develops a trait: they are discordant

• Greater concordance in monozygotic than dizygotic = genetic control

Concordance in twins (table)

• ABO blood type: monozygotic (100%) > dizygotic (66%) = 100% genetic control

• Migraines: monozygotic (62%) > dizygotic (34%) = genetics and environment

• Chicken pox: monozygotic (13%) = dizygotic (15%) = environmental control

Genetic Testing (When is it done?)

• Prenatal - before birth

• Postnatal - after birth and later

• Pre-implantation - in vitro fertilization

Prenatal - Amniocentesis and CVS

• Common test - reliable results

• Lots of genetic fluid

• Risk to mother and fetus

• Slow and late in gestation

Prenatal - Cell-Free DNA Test

• Prenatal, non-invasive screening

• Low risk

• Higher error - not sufficient without other tests

Postnatal - examples

• Newborn screening: genetically based, detected quickly and treated

• Heterozygote screening: non-affected parents, see if child will be affected

• Presymptomatic screening: disease develops late in life, common for genetic counselors

Postnatal - Sickle Cell Disease (heterozygote screening)

• Can perform PCR to see chance of having offspring with the following traits (genetic couseling)

  • Homozygote (s⁺s⁺) - no symptoms

  • Homozygote (s^as^a) - sickle cell anemia

  • Heterozygote (s⁺s^a) - no disease, but occasional mild anemia (= normal phenotype)

How valuable is it to test for diseases with no treatment?

Some diseases are easy to detect and have treatments, other harder to detect or have no treatments.

Pre-Implantation

• Very expensive, no guarantee

• Can choose only girl/boy at extra cost

• Ethical concerns

Genetic Counseling

• Genetic testing and how to deal with results

• Combines the science behind genetics and the counseling aspect of how to deal with the results

23 & Me and other consumer genetic tests

• Some companies selling genetic data to drug companies

• Genetic info. nondiscrimination act: health insurance companies and employers cannot discriminate, or change rates based on genetic tests