Lecture 5 - Non-Mendelian Patterns of Inheritance

Mendel's laws: basic idea (review)

Genetic units (genes) exist in pairs

Law of Dominance (review)

If the two alleles at a locus differ, the dominant allele determines the organism's appearance; the recessive allele has no noticeable effect on appearance

Law of Segregation (review)

The two (homologous) alleles for a heritable character separate during gamete formation and end up in different gametes

Law of Independent Assortment (review)

When looking at two or more pairs of alleles, each pair segregates independently of the other pairs during gamete formation

Three steps of a Punnett square

1) Determine all possible gamete genotypes; 2) Draw the square and place one parent's gametes on top and the other's on the left side; 3) Fill in each square with the alleles from each gamete

What does a Punnett square predict?

All possible combinations of genotypes for the offspring

Gg × gg Punnett square (review)

Gametes: G and g from Gg; g and g from gg; offspring 50% Gg and 50% gg

Mendel's laws and meiosis: replication

RrYy cell replicates its chromosomes before meiosis

Mendel's laws and meiosis: metaphase I

Homologous chromosome pairs line up randomly, then homologous chromosomes segregate

Mendel's laws and meiosis: metaphase II

Sister chromatids line up, then sister chromatids segregate

Gametes of RrYy and why

RY, Ry, rY, ry (25% each), because genes on different chromosomes align randomly at the metaphase plate in meiosis I

Non-Mendelian inheritance

Inheritance patterns that do not follow Mendel's laws

Three conditions for Mendel's laws

1) A trait is determined by only one pair of alleles ("unit factors"); 2) Segregated alleles are distributed randomly and independently into gametes, so genes must be on different chromosomes; 3) One allele must be completely dominant over the other

Five limitations of Mendel's laws

1) Complete dominance does not always occur (co-dominance); 2) Blending inheritance (incomplete dominance); 3) Genes on the same chromosome (linkage); 4) Non-allelic gene interactions such as epistasis, inhibiting factors, complementary genes, and additive factors; 5) A trait may be determined by multiple genes

13 types of non-Mendelian inheritance

1) Incomplete dominance; 2) Co-dominance; 3) Genetic linkage; 4) Multiple alleles; 5) Epistasis; 6) Sex-linked inheritance; 7) Extra nuclear inheritance; 8) Polygenic traits; 9) Gene conversion; 10) Infectious heredity; 11) Genomic imprinting; 12) Mosaicism; 13) Trinucleotide repeat disorder

Who discovered incomplete dominance?

German botanist Carl Correns (1864-1933)

Incomplete dominance

One allele is not completely dominant over another; the heterozygous phenotype is a blending of the two homozygous phenotypes

Principle of uniformity

All offspring in the F1 generation have the same genotype and phenotype; it still works in incomplete dominance

Incomplete dominance example: flower color

C^R C^R = red; C^W C^W = white; C^R C^W = pink (blend of the two alleles)

Incomplete dominance: F1 and F2

F1: all C^R C^W (pink); F2 from pink × pink: 1 red : 2 pink : 1 white (1:2:1 ratio)

Incomplete dominance example: hair

Straight hair (homozygous) + curly hair (homozygous) → wavy hair (heterozygous, a mix of straight and curly)

Why is the incomplete dominance F2 ratio 1:2:1 and not 3:1?

Because the heterozygote has its own intermediate phenotype, so genotype and phenotype ratios are the same

Co-dominance

Two alleles are both expressed as a dominant phenotype at the same time; neither is dominant or recessive, and they do not blend in the phenotype

Co-dominance example: cow coat color

RR = red; WW = white; RW = roan (white with red spots, NOT pink)

Co-dominance vs incomplete dominance (key difference)

Co-dominance: both alleles show equally and are NOT mixed (e.g., red and white patches); Incomplete dominance: alleles are MIXED together (e.g., pink)

Allele (as defined on the co-dominance slide)

One of two or more alternative forms of a gene that arise from mutation

Incomplete dominance flower explanation

If red were completely dominant over white, heterozygotes would be red; because red is only incompletely dominant, the white shows through and the flower is a lighter pink

Petunia example: incomplete vs co-dominance

Red × white petunia: incomplete dominance gives pink flowers; co-dominance gives red and white striped flowers

Co-dominance vs incomplete dominance: definition

Co-dominance: offspring receive both parent genes expressed as a combination; Incomplete dominance: neither parent gene is fully expressed, but a combination is

Co-dominance vs incomplete dominance: effect of the hybrid

Co-dominance: independent effect; Incomplete dominance: intermediate of the two alleles

Co-dominance vs incomplete dominance: effect of the allele

Co-dominance: both alleles equally conspicuous; Incomplete dominance: one allele more conspicuous than the other

Co-dominance vs incomplete dominance: expressed phenotype

Co-dominance: both parental characteristics expressed; Incomplete dominance: none of the parental characteristics, the phenotype is a novel one

Co-dominance vs incomplete dominance: quantitative effect

Co-dominance: absent; Incomplete dominance: present

Who first described genetic linkage?

William Bateson and R. C. Punnett in the 1900s

Genes on non-homologous chromosomes

Assort independently during meiosis

Linked genes

Genes on the same chromosome; they and the traits they control are inherited together because they are on the same chromosome

Thomas Morgan and linkage

Gave the modern understanding of genetic linkage; showed that two recessive fruit fly genes, white eye (w) and miniature wing (m), are X-linked

Separating genes on different vs the same chromosome

Genes on different chromosomes (A and B) are easily shuffled into different gametes; genes on the same chromosome (C and D) can only be separated by crossing over

Morgan's fruit fly cross

BbVgvg (gray, normal wing) × bbvgvg (black, vestigial wing), published 1912

Fruit fly body color alleles

B (wild-type gray body) is dominant over b (black body)

Fruit fly wing alleles

Vg (wild-type normal wing) is dominant over vg (vestigial, very small wing)

Morgan's expected result if Mendel's laws applied

BbVgvg makes BVg, Bvg, bVg, bvg gametes (25% each); bbvgvg makes only bvg; offspring 1:1:1:1 gray normal : gray vestigial : black normal : black vestigial

Morgan's actual result

Genes did not assort independently; they were usually inherited together, so most offspring showed one of the two parental phenotypes

Why did some of Morgan's flies show recombinant phenotypes?

Homologous chromosomes physically exchanged corresponding segments during prophase I of meiosis (crossing over)

Crossing over

Exchange of corresponding segments between homologous chromosomes during prophase I of meiosis

How many chromatids does each crossover involve?

Two of the four chromatids, one from each member of the homologous pair; it can occur anywhere along the chromosome

Why do both chromatids become recombinant?

Segments are exchanged reciprocally, so each chromatid ends up with genes from both of the organism's parents

Tetrad

A pair of homologous chromosomes (4 chromatids) during meiosis I, where crossing over occurs

When does recombination occur?

During prophase I of meiosis

How many recombinant gametes does one crossover make?

Two recombinant gametes (plus two parental gametes)

Morgan's test cross results (2,300 offspring)

Parental: black vestigial 944, gray normal 965; Recombinant: gray vestigial 206, black normal 185

Morgan's recombination frequency

391 recombinants ÷ 2,300 total offspring = 0.17 (17%)

Parental vs recombinant genotypes in Morgan's cross

Parental: b vg and B Vg; Recombinant: B vg and b Vg

Maximum theoretical recombination frequency for two linked genes

50%; at that point the genes behave as if they assort independently

Why is recombination frequency greater for loci farther apart?

Crossing over is more likely to occur between genes that are far apart

How was the fruit fly gene map made?

Using recombination frequencies from test crosses involving various pairs of the genes

Fruit fly chromosome map (5 genes)

Yellow body (y) 0; white eye (w) 1; vermilion eye (v) 31; miniature wing (m) 34; rudimentary wing (r) 58

Unit of genetic map distance

Map units, also called centimorgans (cM)

Why are y and w close on the map?

The recombination frequency between y and w is low

Why are y and v far apart on the map?

Recombination between y and v is more frequent

Practical use of linkage

Allows biologists to isolate genes and create genetic markers linked to important genes, making it easy to identify individuals carrying certain alleles

Multiple alleles

A gene that exists in several different forms in nature (more than two alleles)

Alleles per gene in Mendelian inheritance

Only two (e.g., A and a); Mendel deliberately chose traits with two alleles

What produces multiple alleles?

Gene mutations

Maximum number of alleles some genes may have

As many as 300

How many multiple alleles can one individual carry?

A diploid organism can have any two; a haploid organism or a gamete has just one

Multiple alleles example: rabbit coat color alleles and phenotypes

C (CC) = wild type, brown fur; c^ch (c^ch c^ch) = chinchilla, black-tipped white fur; c^h (c^h c^h) = Himalayan, white fur with black paws, nose, ears, and tail; c (cc) = albino, white fur

Order of dominance: rabbit coat color

C > c^ch > c^h > c

ABO blood type system

An example of multiple alleles in humans: three alleles in the population (I^A, I^B, i), but each person gets only two

What does each ABO allele code for?

I^A: A molecules on red blood cells; I^B: B molecules on red blood cells; i: no molecules on red blood cells

What determines the number of ABO phenotypes?

The dominance relationships between the three alleles

ABO dominance relationships

I^A and I^B are co-dominant with each other; both are dominant over i

ABO genotypes and blood types

Type A: I^A I^A or I^A i; Type B: I^B I^B or I^B i; Type AB: I^A I^B; Type O: ii

Molecular basis of ABO

All start with the H antigen; A gene enzyme (N-acetylgalactosaminyl transferase) adds GalNAc to make A antigen; B gene enzyme (galactosyl transferase) adds galactose to make B antigen; O gene makes no enzyme, so only H antigen remains

Epistasis

A relationship between genes where an allele of one gene hides/masks the visible output (phenotype) of another gene

Effect of epistasis on dominant alleles

It can make it impossible for even dominant alleles at other gene loci to affect the phenotype

Epistasis example: dog coat color

Being homozygous ee at the Extension locus makes it impossible to produce any pigment except pheomelanin (yellow-red)

Why is ee in dogs epistatic even though e is recessive?

Two copies of e override the dominance of other coat color genes

Dog coat color pathway

Yellow (X) → Enzyme E (from E allele) → Chocolate (Y) → Enzyme B (from B allele) → Black (Z)

Dog coat color alleles

E (active) is dominant over e (inactive); B (active) is dominant over b (inactive)

Dog coat color genotypes and phenotypes

E_B_ = black; E_bb = chocolate; ee__ = yellow (9 black : 3 chocolate : 4 yellow)

Eumelanin vs pheomelanin

Eumelanins: brown/black pigments; Pheomelanins: lighter (yellow-red) pigments

Recessive epistasis (9:3:4)

Recessive alleles at one locus mask the expression of both alleles (dominant and recessive) at another locus

Dominant epistasis (12:3:1)

A dominant allele at one locus can mask the expression of both alleles (dominant and recessive) at another locus

Duplicate recessive epistasis (9:7)

Recessive alleles at either of the two loci can mask the expression of dominant alleles at both loci

Duplicate dominant epistasis (15:1)

A dominant allele at either of two loci can mask the expression of recessive alleles at both loci

Duplicate gene interaction (9:6:1)

Two dominant alleles have a similar effect when separate but an enhanced effect when together

Dominant and recessive epistasis (13:3)

A dominant allele at one locus can mask the expression of both alleles at a second locus (listed ratio 13:3)

Recessive epistasis example: mouse coat color

AaBb × AaBb → 9 black (A_B_) : 3 brown (A_bb) : 4 white (aa__); aa masks both alleles at locus B

Mouse coat color pathway

White (X) → Enzyme A (gene A) → Brown (Y) → Enzyme B (gene B) → Black (Z)

Dominant epistasis example: squash color

WWYY (white) × wwyy (green) → F1 WwYy (white); F2: 12 white (W___) : 3 yellow (wwY_) : 1 green (wwyy)

Epistatic gene in squash

W is epistatic; dominant W masks the effect of dominant Y

Duplicate recessive example: pea flower color

AAbb (white) × aaBB (white) → F1 AaBb (all purple); F2: 9 purple (A_B_) : 7 white (3 A_bb, 3 aaB_, 1 aabb)

Pea flower color pathway (duplicate recessive)

Colorless precursor 1 → Allele A (pigment change catalyzed) → Colorless precursor 2 → Allele B (pigment change completed) → Purple pigment; both A and B are needed for purple

Duplicate dominant example: Shepherd's purse (Capsella)

TTVV (triangular seeds) × ttvv (ovate seeds) → F1 TtVv (all triangular); F2: 15 triangular : 1 ovate

Why are some Shepherd's purse seeds ovate?

Seed shape is normally triangular; ovate seeds only come from a double gene knockout (tt vv)

Who described sex-linked inheritance?

Thomas Hunt Morgan (1910)

Does sex affect Mendel's crosses?

No; but Mendel's laws do not apply to genes located only on the X or Y chromosome

Sex-linked inheritance

Inheritance of a trait determined by a gene located on one of the sex chromosomes

X-linked or Z-linked genes

Genes found only on the X chromosome, or on the analogous Z chromosome in birds and some other species