bio 207 lec 12
What are three major challenges in studying human genetics?
Controlled matings are not possible
→ We can’t do test crosses like in model organisms.
Humans have long generation times
→ ~20 years vs. 2 weeks for fruit flies (Drosophila).
Small family sizes
→ Too few offspring to observe Mendelian ratios (e.g., 9:3:3:1).
What is a pedigree?
A pictorial family tree showing the inheritance of specific traits across generations.
What is a proband in a pedigree?
The first family member studied for a trait. Marked with “P” and an arrow.
How are generations and individuals labeled in pedigrees?
Generations: Roman numerals (I, II, III…)
Individuals: Numbers within a generation (1, 2, 3…)
In a pedigree, what do horizontal and vertical lines represent?
Horizontal line = mating between mother and father
Vertical line = connects parents to their children (progeny)
How are children labeled in a pedigree?
Children are numbered in ascending order (1, 2, 3...) within each generation.
How is sex shown in a pedigree?
Males = squares
Females = circles
Unknown sex = diamond
Shaded = affected by the trait
What is an obligate carrier?
A person who carries the mutant allele but does not show the trait. Shown with a dot in the center of the symbol.
How do autosomal recessive traits appear?
Equal in both sexes
Only in homozygous individuals (aa)
Often skip generations
if an autosomal recessive trait is rare, what is expected?
If trait is rare, affected offspring
likely have heterozygous parents
and traits skip a generation
What increases the chance of an autosomal recessive trait showing up?
Consanguinity — mating between close relatives (e.g., cousins).
Key features of autosomal dominant traits?
Appear in both sexes equally
Don’t skip generations
Only one copy of mutant allele needed
Example of an autosomal dominant disorder?
Familial hypercholesterolemia
LDL (low-density lipoproteins) receptor defect (mutation) → high cholesterol
Heterozygotes: heart attacks by 35, blood LDL levels twice regular
Homozygotes: heart attacks in childhood (2-20), blood LDL levels 6 times the regular
Key signs of X-linked recessive inheritance?
More males affected
Passed from carrier mothers to sons
Never passed father → son
What is hemophilia A an example of?
An X-linked recessive disorder caused by a mutation in a gene on X chromosome leading to reduced clotting factor VIII --> excessive bleeding (even small cuts are life threatening)
Why might a heterozygous female show mild symptoms of hemophilia A?
Due to random X-inactivation, more of her normal Xs may be inactivated, leaving mutant Xs active in more cells.
Severity of hemophilia is proportional to number of cells
with active Xh
Key features of X-linked dominant traits?
Affects both sexes
Doesn’t skip generations
Affected fathers: all daughters affected, no sons affected
Heterozygous mothers: pass to half sons and half daughters
Example of X-linked dominant disorder?
Hypophosphatemia (Vitamin D-resistant rickets)
Mutation in PHEX gene
Affects bone development due to phosphate loss (bone deformities, stiff spines and joints, bowled legs, mild growth deficiencies)
What does the PHEX gene normally do?
It suppresses FGF-23 (fibroblast growth factor 23), a hormone that regulates phosphate levels in the blood. High FGF-23 leads to low levels of phosphate in blood (high excretion via
kidneys)
What happens when PHEX is mutated?
FGF-23 becomes overactive
This causes excess phosphate loss via the kidneys
Result = low phosphate levels, which impairs bone and tooth development
What could be a possible treatment target for Hypophosphatemia?
lowering FGF-23 activity --> Enhancing phosphate retention
✅ Targeting FGF-23 directly or mimicking PHEX function could restore phosphate balance. Gene therapy is still in its infancy, but maybe one day we can fix the mutation via CRISPR .
Easiest solution would be to make an antagonist for
FGF-23, to reduce it’s level back to normal range
What are Y-linked traits?
Traits passed only from father to son because they are found only on the Y chromosome. do not skip gens.
Are Y-linked traits dominant or recessive?
Neither — males have only one Y, so the trait is always expressed if present.
gene-environment interaction (major challenge in genetics)
Traits and Gene expression (which genes, when, how much) are affected by the environment the organism develops and resides in
Why are twin studies useful in genetics?
They provide a natural experiment to separate genetic and environmental influences on traits.
What are monozygotic twins?
Also called identical twins, they come from one fertilized egg that splits early. They are genetically identical and share 100% of their alleles.
4/1000 - rare
What are dizygotic twins?
Also called fraternal twins, they come from two separate eggs fertilized by two sperm. They share about 50% of their genes, like typical siblings.
What is concordance in twin studies?
Concordance is the percentage of twin pairs in which both twins express the same trait.
If only one twin has it, they are discordant.
How does concordance show genetic influence?
If a trait shows higher concordance in monozygotic than dizygotic twins, it suggests the trait is genetically influenced.
What did the asthma twin study show?
Monozygotic twins: 65% concordance
Dizygotic twins: 37% concordance
✅ Shows a genetic component, but the 37% in DZ twins shows environment also plays a role.
What does higher concordance for epilepsy and rheumatoid arthritis in monozygotic twins suggest?
That both traits are genetically influenced — monozygotic twins show much higher concordance than dizygotic twins.
🧪 From the data:
Epilepsy: 59% (MZ) vs 19% (DZ)
Rheumatoid arthritis: 32% (MZ) vs 6% (DZ)
What do adoption studies help separate?
The effects of genes vs. environment on traits by observing children raised apart from biological parents.
What does it mean if an adopted child shares a trait with their biological parent?
The trait is likely genetically influenced.
What does it mean if an adopted child shares a trait with their adoptive parent?
The trait is likely influenced by the environment.
Example trait studied in adoption studies?
BMI and obesity — shown to have a strong genetic component.
What is genetic counseling?
A field that provides information and support to patients about genetic conditions and risks, often using family history, genetic tests, and medical exams.
What professionals are involved in genetic counseling?
Genetic counselors, physicians, geneticists, and lab specialists.
What are the key steps in genetic counseling after a patient is diagnosed? (7)
hysical examination
Biochemical tests
DNA testing
Chromosome analysis
Family history review
Physician determines the genetic cause
Appropriate treatment is recommended
What is the goal of genetic testing?
To detect potential genetic conditions early for:
Reproductive decision-making
Early intervention
Reducing anxiety
What are the two types of genetic testing timing?
Prenatal (before birth)
Postnatal (after birth)
how many disorders can prenatal testing look diagnose
Currently include procedures
to diagnose hundreds of
genetic disorders and
diseases
What is ultrasonography and how is it used in prenatal testing?
Ultrasonography (ultrasound) uses high-frequency sound waves to create images of the fetus by detecting differences in tissue density.
Is ultrasound invasive or non-invasive?
Non-invasive — it poses no risk to the fetus or mother.
What types of genetic conditions can be detected by ultrasound?
Neural tube defects
Skeletal abnormalities
Developmental disorders
What is amniocentesis?
A test that collects amniotic fluid for chromosomal, biochemical, or DNA analysis.
disadvantages:
performed 15–18 weeks into pregnancy
culturing takes more time
Invasive with a small risk of miscarriage
What is chorionic villus sampling (CVS)?
A test that collects cells from the chorion (placental tissue-fetal cells) earlier in pregnancy (10–12 weeks).
Faster, but still invasive.
What is non-invasive prenatal screening (NIPS)? hong kong, 2001
A method that uses maternal blood. (testing for chemical substances in blood)
Can detect aneuploidies and sex chromosome abnormalities as early as 10 weeks.
✅ No risk to fetus
What is cell-free fetal DNA testing and how does it work?
During pregnancy, fetal cells release DNA fragments into the mother’s bloodstream. This cell-free fetal DNA (cffDNA) makes up about 3.4–6.2% of maternal blood.
What can cffDNA be used to test for?
Aneuploidy (e.g., Down syndrome, trisomy 18)
Sex chromosome anomalies (e.g., Turner syndrome, Klinefelter syndrome)
Other chromosomal abnormalities
What disorders can prenatal testing detect?
Chromosome abnormalities (via karyotyping)
Hemophilia, cystic fibrosis, Tay-Sachs, sickle cell anemia, cleft palate, etc.
What is newborn screening?
Postnatal testing for certain genetic disorders in newborns so early treatment can begin.
📍 In Alberta: screens for metabolic, endocrine, and immune disorders, plus cystic fibrosis and spinal muscular atrophy. (sickle cell disease/ severe combined immunodeficiency)
What is pharmacogenetic testing?
A test to see how a person's genes affect drug response, helping to choose the best treatment and avoid side effects.
What is genetic mosaicism?
When an individual has two or more genetically distinct cell lines, often due to mixing of cells during early embryonic development.
Why is genetic mosaicism important in testing?
It can lead to different genetic test results depending on which tissue the sample is taken from — important for forensics and diagnostics.