Topic F

Question 1

Simple Inheritance vs complex inheritance

Answer 1

Simple inheritance
- One, or a small number of genes q Qualitative traits
- Discontinuous variation
- Relatively easy to study

Complex inheritance
- A larger number of genes
- Quantitative traits
- Continuous variation q Challenging to study

Most phenotypes in multicellular eukaryotes are not determined by simple inheritance.
- Eye color in humans – at least sixteen genes
- Type 1 Diabetes, >50 genetic loci
- Breast cancer >170 genetic loci

Question 2

Simple Inheritance

Answer 2

Simply inherited single gene traits exhibit one of four inheritance patterns

• Genes on autosomes (chromosomes that are not sex chromosomes)
  — Autosomal Dominant
  — Autosomal Recessive
• Genes on the sex chromosomes
  — Sex-linked Dominant
  — Sex-linked Recessive

Sex biological differences
- chromosomes
- genes
- hormones

Gender
Social and cultural differences
- behaviour
- identity
- norms
- roles

Question 3

There are different mechanisms by which biological sex is determined, but all mechanisms depend on differences in gene expression

Answer 3

• Sex chromosomes
• Egg incubation temperature in some reptiles (alligators, sea turtles)
• Social dominance in clown fish

2 of same chromosome are homochromatic

Question 4

Autosomal inheritance in model organisms

Answer 4

• Autosomal inheritance and reciprocal crosses
• Mendel studied simply inherited autosomal traits

1st half
Round dom to wrinkled

P1 R/R (m) x r/r (f)

F1 R/r (mono hybrid, hetero)

F2 3:1 phenotypic ratio of round to wrinkled

Now the reciprocal cross flip the phenotypes
Second half

P1 r/r (m) x R/R (f)

F1 R/r

F2 3:1 round : wrinkled

Question 5

Sex-linked inheritance in model organisms

Thomas Hunt Morgan & Lilian Vaughan Morgan

Answer 5

Early 1900s
Medals experiments rediscovered

The white (w) mutation in Drosophila

Initial parental cross:

Crossed red-eyed ♀ to white-eyed ♂ parents

F1: All red eyed ♀ and ♂

F2: Expected phenotypic ratio… (♀ and ♂)
If it was autosomal 3:1 red:white

Observed… (♀ vs. ♂) 100% red females and 50/50 red/white males

Hypothesis:
Doesn’t conform to Mendelian genetics

Therefore white eye gene is on X chromosome

Question 6

Allele notation for sex chromosomes

Answer 6

X^w+/X^w+

X^w// Y

Have to note if on X or Y chromosome

+ means it’s the wild type or dom? If it doesn’t have + it’s the rec one

Question 7

Contributions of X-linked studies

Answer 7

This research confirmed the chromosome theory of heredity
- Inheritance of this gene could be directly linked to the transmission of X and Y chromosomes

It also provides a critical example of X-linked inheritance patterns
- Different phenotypes or ratios in the F1 and F2 generations of reciprocal crosses
- Different patterns of inheritance in ♀ and ♂

Question 8

Review of Concepts

Answer 8

• Morgan’s research supported the chromosome theory of heredity
• Distinct symbolism is used for alleles on sex chromosomes
• X-linked genes show distinct patterns of inheritance in ♂ vs.♀ because ♂ have only one allele while ♀ have two alleles q where ♀ are the homogametic sex & ♂ the
  heterogametic sex
• Different phenotypic ratios in ♂ vs. ♀ (gender bias) and different phenotypic ratios in the F1 and F2 generation of reciprocal crosses are observed with sex-linked, but not with autosomal, traits
• Be aware that different mechanisms of sex determination exist

Question 9

Pedigree Analysis

Why is studying inheritance in humans so challenging?

Answer 9

Polygenic genes

Complex inheritance

Genome very large

Environmental factors can turn alleles off or on

Very expensive to care for humans

Confounding Environmental conditions

Medical ethics

No true breeding humans

Long generational times

Small family sizes in humans

Lack of complete family history

Question 10

Pedigree Analysis

Answer 10

Four patterns of simple genetic inheritance

• Autosomal vs. Sex-linked
• Dominant vs. Recessive

What is a pedigree?
- Family tree in which a particular trait is followed
- Needs a detailed family history

Pedigree analysis
- Is there evidence of a particular mechanism of
inheritance?
- Means that many many pedigrees of different families are needed

Circle female
Square male
Not coloured in is unaffected individuals
Coloured in is affected individuals

Question 11

When carrying out pedigree analysis keep in mind the following:

Answer 11

1. Genetic disorders/diseases are rare
2. Mendelian ratios are rarely seen in a pedigree
3. Non-family members are assumed to be homozygous unaffected (unless there is compelling evidence to the contrary)
4. Recessive disorders are more common than dominant ones
5. Most human traits do NOT demonstrate simple inheritance

Question 12

Always ask two questions of each pedigree:

Answer 12

1. Do two unaffected individuals ever produce an affected child

• If yes, then the trait is most likely recessive
• If no (affected children always have an affected parent) then the trait is most likely dominant

2. Is there any clear sex bias present

• Yes, there is evidence of sex bias. The trait is most likely sex-linked
  — If the trait is X-linked recessive we see all (or almost all) males affected
  — If the trait is X-linked dominant, an affected male will produce all affected daughters and no affected sons; whereas an affected female will pass on the trait equally to both males and females
  — If the trait is Y linked males will pass it on only to sons, females will not have it
• No, there is no evidence of sex bias. The trait is most likely autosomal.

Question 13

Pedigree Analysis

Evidence that suggests an autosomal dominant disorder:

Answer 13

P1 A/a (m) x a/a (f)

F1 a/a (m). A/a (f). a/a (m). A/a (m)

A = affected
a = unaffected

1. Do see unaffected parents produce affected offspring?
   - no, suggest dom trait
2. Sex bias?
   - father 1 to son and daughter
   - no sec bias being shown

Assume ppl who married into family are homo rec.

Therefore autosomal dominant

Question 14

Pedigree Analysis

Evidence that suggests an autosomal recessive disorder:

Answer 14

P1 A/a (m). X. A/a (f)

F1 a/a (m) a/a (f)

A = unaffected
a = affected

1. Unaffected parent produce affected offspring?
   - yes, suggest recessive

Only way could be affected if get 1 from mom and dad

2. Sex bias?
   - doesn’t have strong bias

Therefore it’s autosomal recessive

Question 15

Pedigree Analysis

Evidence that suggests an X-linked Dominant disorder:

Answer 15

P1 X^a / X^a x X^A/Y

F1 have 2 X^A/X^a and 2 X^a/Y

A = affected
a = unaffected

1. Unaff parent produce affe offspring
   - no
2. Sex bias?
   - yes. Father only daughters affected
   - mother offspring equally affected son and daughter

Question 16

Pedigree Analysis

Evidence that suggests an X-linked recessive disorder:

Answer 16

P1 X^A/X^— x X^a/Y

F1 none affected

F2 X^a/Y

A = unaffected
A = affected

1. Unaffect parent produce aff offspring
   - yes rec
2. Sex bias?
   - only males even tho only 2 cases, so X-linked
   - No Y linked b/c it goes through the mother

Question 17

Pedigree Analysis

Y-linked

Answer 17

• Y = hemizygous
• Pseudoautosomal region
• Evidence that suggests an Y-linked trait

Don’t have a lot of homo chrome for Y

Therefore don’t use dom or rec

Usually seen in 2ndary sex characteristics

Only in males, sterilization is caused

Question 18

Summary

Answer 18

• Understanding inheritance in humans is often challenging; however, when a detailed family history of the inheritance of a disorder exists, we can often determine the mechanism of inheritance by carrying out pedigree analysis.
• Observations such as whether unaffected parents have affected children indicate whether the inheritance pattern is dominant or recessive.
• Observations such as whether males are affected differently than females are often indicative of whether the trait is sex-linked or autosomal