1. Pedigree Analysis
Recognizing different patterns of inheritance within different types of pedigrees
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When geneticists want to learn about the inheritance of human traits, they collect information about a family’s history – then use it to create a pedigree.
Pedigrees are visual tools that can help determine a particular pattern of inheritance.

2. Tee hee
Studying human genetics relies on family history – not experimental crosses.

3. What is a Pedigree?
Diagram or flowchart that uses symbols to show patterns of relationships & traits in a family over many generations
4 patterns of inheritance to be analyzed:
Autosomal recessive
Autosomal dominant
Sex-linked recessive
Sex-linked dominant
The study of human genetics and inheritance lies largely in analysis of family history (we cannot produce thousands of offspring like plants or flies and we can’t do experimental crosses between two individuals!!!)

4. Symbols in Pedigree Charts
Standard symbols are used to make pedigrees universal.
Male = square; Female = circle
Shaded = HAVE the condition
Unshaded = DO NOT HAVE
Half-shaded or dot = heterozygote or carrier. Carries the recessive allele but does NOT express the trait/condition.

5. Symbols in Pedigree Charts
Oldest (first generation) at top, youngest at the bottom – signified by roman numerals
Generally older individuals to the left.
Horizontal line between two individuals indicates mating/marriage. Vertical line = generation change.
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6. Examples Dominant sex-linked Recessive autosomal Dominant autosomal
Dominant sex-linked
Recessive autosomal
Based on these four patters, a condition could be dominant OR recessive, autosomal OR sex-linked.
Dominant autosomal
Recessive sex-linked

7. Allele Notation
Dominant autosomal trait: the affected allele = “A” and the unaffected allele =“a”
Recessive autosomal trait: the affected allele = “a” and the unaffected allele = “A”
Dominant sex-linked trait: the affected allele = “XA” and the unaffected allele = “Xa”
Recessive sex-linked trait: the affected allele = “Xa” and the unaffected allele = “XA”
Depending on whether the condition is dom/rec and auto/sex, we symbolize the alleles accordingly.

8. Pedigree Analysis
Step 1: Determine whether the trait demonstrated by the pedigree is dominant or recessive Step 2: Determine whether the trait is sex-linked or autosomal. To do this, you must look for evidence of certain patterns of inheritance.

9. The Pedigree Decision Tree
These are the steps we will take every time.

10. Step 1: Dominant or recessive?
Use the decision tree and look for evidence!
Recessive?
1) Kids have the condition but parents DON’T
You see heterozygotes (they are shown)
Dominant?
1. Every affected kid has at least one affected parent.

11. Why do heterozygotes indicate a recessive trait?
Heterozygote = carries the gene but does not display the trait If recessive trait, an individual with Aa will appear as this If dominant trait, an individual with Aa will appear as this: OR
Remember, for recessive traits, recessive phenotypes ONLY show up in homozygous form.
A dominant allele can mask or hide a recessive one.

12. Dominant or recessive?
Recessive! Unaffected parents produce affected offspring

13. Dominant or recessive?
Easy to track. Affected parents passing it on to kids.
Dominant! All affected individuals have an affected parent

14. Dominant or recessive?
Recessive! Heterozygotes AND unaffected parents produce affected offspring

15. Remember the steps:
Step 1: Determine whether the trait demonstrated by the pedigree is dominant or recessive
Once you do this, you are ready to go to step 2!
Step 2: Determine whether the trait is sex-linked or autosomal.
- The evidence you look for depends on your answer for step 1
ALWAYS start with dominant/recessive – then go from there.

16. The Pedigree Decision Tree

17. For recessive pedigrees Step 2: Autosomal or sex-linked?
Use the decision tree and look for evidence!
If the disorder/trait is receissive, a parent doesn’t have to HAVE (show) the disorder to pass it on to their kids.

18. For recessive pedigrees Step 2: Autosomal or sex-linked?
RECESSIVE AUTOSOMAL if:
Male carriers/heterozygotes
Affected female has unaffected parents
RECESSIVE SEX-LINKED if:
If carrier mother x unaffected father has affected son
No affected females, suspect sex-linked
If it is recessive, look at affected females…
A recessive trait in females MUST be passed on to sons (if it is X-LINKED !!!)
If a recessive female does NOT pass it on to her son, it is AUTOSOMAL.

19. Example

20. 1) Recessive or Dominant? 2) Autosomal or Sex-Linked?
Recessive! Unaffected parents produce affected offspring
Autosomal! Unaffected parents produce affected daughter
E.g. Phenylketonuria (PKU)  1/12,000 live births homozygous for PKU
gene that codes for an enzyme required to convert phenylalanine  x  y  tyrosine is defective or absent resulting in accumulation of neurotoxic intermediates causes cognitive delay
treatment – low phenylalanine diet
metabollic disorder having to do with protein metabolism. A certain amino acid (phenylalanine) is converted to phenylpyruvic acid cause an enzyme is missing and this acid is toxic so it results in mental retardation. Low protein diet will help.
1,000 different mutations in the CFTR (cystic fibrosis transmembrane conductance regulator gene) have been identified. most common mutation (observed in 70% of cystic fibrosis patients) is a three-base deletion in the DNA sequence, causing an absence of a single amino acid in the protein product.
affects the respiratory and digestive systems. inherit a defective gene on chromosome 7 called CFTR. The protein produced by this gene normally helps salt (sodium chloride) move in and out of cells. If the protein doesn't work correctly, that movement is blocked and an abnormally thick sticky mucous is produced on the outside of the cell. The cells most seriously affected by this are the lung cells. mucous clogs the airways in the lungs, and increases the risk of infection by bacteria such as Pseudomonas aeruginosa.
mucous also blocks ducts in the pancreas, so digestive enzymes can't get into the intestines. intestines cannot properly digest food. `do not get the nutrition they need to grow normally.
advanced cases need lung transplant, supplement diet with digestive enzymes. mostly physical therapy exercises to clear mucous.

21. Example

22. 1) Recessive or Dominant? 2) Autosomal or Sex-Linked?
Recessive! Heterozygotes AND unaffected parents produce affected offspring
Carrier mother x unaffected father producing affected sons
More common in males – females are mostly carriers.
No male to male transmission.

23. For dominant pedigrees Step 2: Autosomal or sex-linked?
Use the decision tree and look for evidence!

24. For dominant pedigrees Step 2: Autosomal or sex-linked?
IF DOMINANT, the pedigree must be DOMINANT AUTOSOMAL if:
Affected father has unaffected daughter
Affected father has affected son with unaffected mother
DOMINANT SEX-LINKED if:
Affected father has all affected daughters and no affected sons
Affected kids must have ONE affected parent.
A clue it’s dominant: 2 affected parents have an unaffected kid (parents are heterozygotes).

25. Dominant Autosomal Pedigrees
Affected father has unaffected daughter
Affected father has affected son with unaffected mother
Because father MUST be a carrier  genotype = Aa
Unaffected daughter MUST be aa
Fathers give their X’s to their daughters. Only way fathers can pass to their sons is if it is AUTOSOMAL.
Since the father gives the allele to the son,
it must be autosomal

26. Dominant Sex-Linked Pedigrees
Affected father has all affected daughters and no affected sons XA Y Xa
XAXa
XaY
With a dominant X trait, a dad with the condition will ALWAYS give it to his daughters.
All affected
daughters
No affected
sons

27. Example

28. 1) Recessive or Dominant? 2) Autosomal or Sex-Linked?
Autosomal! Affected father produces unaffected daughters
Father passed it to SON. + No generations are skipped.
Dominant! All affected individuals have an affected parent

29. Example

30. 1) Recessive or Dominant? 2) Autosomal or Sex-Linked?
Dominant! All affected individuals have an affected parent
Sons can only have it if mom does. No male to male transmission.
Sex-linked! Affected fathers produce all affected daughters AND no affected sons

31. The Pedigree Decision Tree

32. Genotyping aa AA or Aa XaXa XAXA or XAXa Dominant autosomal Genotype
Recessive autosomal
Dominant
sex-linked
Recessive sex-linked aa
AA or Aa
XaXa
XAXA or XAXa
Fill in table on notes. Pay attention to the description of the trait.

33. Genotyping aa AA or Aa XaXa XAXA or XAXa XaY XAY Aa XAXa
Dominant autosomal
Genotype
Recessive autosomal
Dominant
sex-linked
Recessive sex-linked aa
AA or Aa
XaXa
XAXA or XAXa
XaY
XAY Aa
XAXa

34. Pedigree Practice Recessive or dominant trait? How can you tell?
Recessive – heterozygotes and unaffected parents with affected kids
Autosomal – heterozygous males.
Recessive or dominant trait? How can you tell?
Autosomal or sex-linked trait? How can you tell?
Identify the genotypes.

35. Pedigree Practice Recessive or dominant trait? How can you tell?
Dominant – all aff. Kids have affected parents
Auto – aff. Dad has unaffected daughters.
Recessive or dominant trait? How can you tell?
Autosomal or sex-linked trait? How can you tell?
Identify the genotypes.

36. Pedigree Practice Dominant – every affected kid has an affected parent
Autosomal – not all of dad’s (I-1) daughters inherited the condition (II-6)

37. Pedigree Practice
Recessive – unaffected parents with affected kids (even though there are no heterozygotes shown)
Autosomal – Affected parents with affected daughter. Because it’s recessive, her dad would HAVE to have it also if it were sex-linked (he would have the recessive X) but he doesn’t.

38. Pedigree Practice Recessive – heterozygotes + skipping generations
Sex-linked – only males affected.

39. Q: did you notice that the last pedigree was the same example from earlier in this lecture?!?

40. Pedigree Practice Dominant – every affected kid has an affected parent
X-linked – affected dads pass it to all daughters, no sons.

41. Chapter 17

42. What you need to know about pedigrees:
How to be able to recognize the patterns of inheritance associated with the four types of pedigrees: dominant autosomal, dominant sex-linked, recessive autosomal, recessive sex-linked