Simple Inheritance vs complex inheritance
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
Simple Inheritance
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
There are different mechanisms by which biological sex is determined, but all mechanisms depend on differences in gene expression
- Sex chromosomes
- Egg incubation temperature in some reptiles (alligators, sea turtles)
- Social dominance in clown fish
2 of same chromosome are homochromatic
Autosomal inheritance in model organisms
- 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
Sex-linked inheritance in model organisms
Thomas Hunt Morgan & Lilian Vaughan Morgan
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
Allele notation for sex chromosomes
Xw+/Xw+
Xw// 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
Contributions of X-linked studies
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 ♂
Review of Concepts
- 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
Pedigree Analysis
Why is studying inheritance in humans so challenging?
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
Pedigree Analysis
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
When carrying out pedigree analysis keep in mind the following:
- Genetic disorders/diseases are rare
- Mendelian ratios are rarely seen in a pedigree
- Non-family members are assumed to be homozygous unaffected (unless there is compelling evidence to the contrary)
- Recessive disorders are more common than dominant ones
- Most human traits do NOT demonstrate simple inheritance
Always ask two questions of each pedigree:
- 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
- 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.
Pedigree Analysis
Evidence that suggests an autosomal dominant disorder:
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
- Do see unaffected parents produce affected offspring?
- no, suggest dom trait - 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
Pedigree Analysis
Evidence that suggests an autosomal recessive disorder:
P1 A/a (m). X. A/a (f)
F1 a/a (m) a/a (f)
A = unaffected
a = affected
- Unaffected parent produce affected offspring?
- yes, suggest recessive
Only way could be affected if get 1 from mom and dad
- Sex bias?
- doesn’t have strong bias
Therefore it’s autosomal recessive
Pedigree Analysis
Evidence that suggests an X-linked Dominant disorder:
P1 Xa / Xa x XA/Y
F1 have 2 XA/Xa and 2 Xa/Y
A = affected
a = unaffected
- Unaff parent produce affe offspring
- no - Sex bias?
- yes. Father only daughters affected
- mother offspring equally affected son and daughter
Pedigree Analysis
Evidence that suggests an X-linked recessive disorder:
P1 XA/X— x Xa/Y
F1 none affected
F2 Xa/Y
A = unaffected
A = affected
- Unaffect parent produce aff offspring
- yes rec - Sex bias?
- only males even tho only 2 cases, so X-linked
- No Y linked b/c it goes through the mother
Pedigree Analysis
Y-linked
- 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
Summary
- 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
