Transcript Pierce chapter 6

Chapter 6 – Pedigree Analysis
and Applications
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
• If woman is affected,
100% of sons will be
affected
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 female will have
100% sons affected
• 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
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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 (1015mg)
– 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