1. Beyond Mendel’s Laws of Inheritance

2. Extending Mendelian genetics
Mendel worked with a simple system
peas are genetically simple
most traits are controlled by a single gene
each gene has only 2 alleles, 1 of which is completely dominant to the other
The relationship between genotype & phenotype is rarely that simple

3. Incomplete dominance
Heterozygote shows an intermediate, blended phenotype
example:
RR = red flowers
rr = white flowers
Rr = pink flowers
make 50% less color
RR
WW
RW RR RW WW

4. It’s like flipping 2 pennies!
Incomplete dominance X P
true-breeding
red flowers
true-breeding
white flowers
100%
100% pink flowers F1
generation
(hybrids)
It’s like flipping 2 pennies!
self-pollinate
25%
white F2
generation
25%
red
1:2:1
50%
pink

5. Co-dominance 2 alleles affect the phenotype equally & separately
not blended phenotype
human ABO blood groups
3 alleles
IA, IB, i
IA & IB alleles are co-dominant
glycoprotein antigens on RBC
IAIB = both antigens are produced
i allele recessive to both

6. Genetics of Blood type A IA IA or IA i B IB IB or IB i AB IA IB O i i
pheno-type
genotype
antigen on RBC
antibodies in blood
donation status A
IA IA or IA i
type A antigens on surface of RBC
anti-B antibodies __ B
IB IB or IB i
type B antigens on surface of RBC
anti-A antibodies AB
IA IB
both type A & type B antigens on surface of RBC
no antibodies
universal recipient O
i i
no antigens on surface of RBC
anti-A & anti-B antibodies
universal donor

7. Pleiotropy Most genes are pleiotropic
one gene affects more than one phenotypic character
1 gene affects more than 1 trait
dwarfism (achondroplasia)
gigantism (acromegaly)
The genes that we have covered so far affect only one phenotypic character, but most genes are pleiotropic

8. Acromegaly: André the Giant

9. Inheritance pattern of Achondroplasia
Aa x aa
Aa x Aa
dominant inheritance a a A a  Aa Aa AA Aa A A
dwarf
dwarf
lethal a aa aa a Aa aa
50% dwarf:50% normal or 1:1
67% dwarf:33% normal or 2:1

10. How would you know that difference wasn’t random chance?
Epistasis
One gene completely masks another gene
coat color in mice = 2 separate genes
C,c: pigment (C) or no pigment (c)
B,b: more pigment (black=B) or less (brown=b)
cc = albino, no matter B allele
9:3:3:1 becomes 9:3:4
B_C_
B_C_
bbC_
bbC_
_ _cc
_ _cc
How would you know that difference wasn’t random chance?
Chi-square test!

11. Epistasis in Labrador retrievers
2 genes: (E,e) & (B,b)
pigment (E) or no pigment (e)
pigment concentration: black (B) to brown (b)
eebb
eeB–
E–bb
E–B–

12. Polygenic inheritance
Some phenotypes determined by additive effects of 2 or more genes on a single character
phenotypes on a continuum
human traits
skin color
height
weight
intelligence
behaviors

13. Johnny & Edgar Winter
Skin color: Albinism
However albinism can be inherited as a single gene trait
aa = albino
albino Africans
melanin = universal brown color
enzyme
tyrosine
albinism
melanin

14. OCA1 albino
Bianca Knowlton

15. Sex linked traits 1910 | 1933 Genes are on sex chromosomes
as opposed to autosomal chromosomes
first discovered by T.H. Morgan at Columbia U.
Drosophila breeding
good genetic subject
prolific
2 week generations
4 pairs of chromosomes
XX=female, XY=male

16. Classes of chromosomes
autosomal chromosomes
sex chromosomes

17. Discovery of sex linkage
true-breeding
red-eye female
true-breeding
white-eye male X P
Huh! Sex matters?!
100%
red eye offspring F1
generation
(hybrids)
100%
red-eye female
50% red-eye male
50% white eye male F2
generation

18. What’s up with Morgan’s flies?x x RR rr Rr Rr  r r R r R Rr Rr R RR Rr
Doesn’t work that way! R Rr Rr r Rr rr
100% red eyes
3 red : 1 white

19. Genetics of Sex X Y X XX XY X XX XY
In humans & other mammals, there are 2 sex chromosomes: X & Y
2 X chromosomes
develop as a female: XX
gene redundancy, like autosomal chromosomes
an X & Y chromosome
develop as a male: XY
no redundancy X Y X XX XY X XX XY
50% female : 50% male

20. Let’s reconsider Morgan’s flies…x x
XRXR
XrY
XRXr
XRY Xr Y XR Y  XR XR
XRXr
XRY
XRXR
XRY
BINGO! XR Xr
XRXr
XRY
XRXr
XrY
100% red females
50% red males; 50% white males
100% red eyes

21. Genes on sex chromosomes
Y chromosome
few genes other than SRY
sex-determining region
master regulator for maleness
turns on genes for production of male hormones
many effects = pleiotropy!
X chromosome
other genes/traits beyond sex determination
mutations:
hemophilia
Duchenne muscular dystrophy
color-blindness
Duchenne muscular dystrophy affects one in 3,500 males born in the United States.
Affected individuals rarely live past their early 20s.
This disorder is due to the absence of an X-linked gene for a key muscle protein, called dystrophin.
The disease is characterized by a progressive weakening of the muscles and loss of coordination.

22. Human X chromosome Sex-linked usually means “X-linked”
Duchenne muscular dystrophy
Becker muscular dystrophy
Ichthyosis, X-linked
Placental steroid sulfatase deficiency
Kallmann syndrome
Chondrodysplasia punctata,
X-linked recessive
Hypophosphatemia
Aicardi syndrome
Hypomagnesemia, X-linked
Ocular albinism
Retinoschisis
Adrenal hypoplasia
Glycerol kinase deficiency
Incontinentia pigmenti
Wiskott-Aldrich syndrome
Menkes syndrome
Charcot-Marie-Tooth neuropathy
Choroideremia
Cleft palate, X-linked
Spastic paraplegia, X-linked,
uncomplicated
Deafness with stapes fixation
PRPS-related gout
Lowe syndrome
Lesch-Nyhan syndrome
HPRT-related gout
Hunter syndrome
Hemophilia B
Hemophilia A
G6PD deficiency: favism
Drug-sensitive anemia
Chronic hemolytic anemia
Manic-depressive illness, X-linked
Colorblindness, (several forms)
Dyskeratosis congenita
TKCR syndrome
Adrenoleukodystrophy
Adrenomyeloneuropathy
Emery-Dreifuss muscular dystrophy
Diabetes insipidus, renal
Myotubular myopathy, X-linked
Androgen insensitivity
Chronic granulomatous disease
Retinitis pigmentosa-3
Norrie disease
Retinitis pigmentosa-2
Sideroblastic anemia
Aarskog-Scott syndrome
PGK deficiency hemolytic anemia
Anhidrotic ectodermal dysplasia
Agammaglobulinemia
Kennedy disease
Pelizaeus-Merzbacher disease
Alport syndrome
Fabry disease
Albinism-deafness syndrome
Fragile-X syndrome
Immunodeficiency, X-linked,
with hyper IgM
Lymphoproliferative syndrome
Ornithine transcarbamylase
deficiency
Human X chromosome
Sex-linked
usually means “X-linked”
more than 60 diseases traced to genes on X chromosome

23. Map of Human Y chromosome?
< 30 genes on Y chromosome
Sex-determining Region Y (SRY)
linked
Channel Flipping (FLP)
Catching & Throwing (BLZ-1)
Self confidence (BLZ-2) note: not linked to ability gene
Devotion to sports (BUD-E)
Addiction to death & destruction movies (SAW-2)
Scratching (ITCH-E)
Spitting (P2E)
Inability to express affection over phone (ME-2)
Selective hearing loss (HUH)
Total lack of recall for dates (OOPS)
Air guitar (RIF)

24. Hemophilia is a sex-linked recessive trait defined by the absence of one or more clotting factors.
These proteins normally slow and then stop bleeding.
Individuals with hemophilia have prolonged bleeding because a firm clot forms slowly.
Bleeding in muscles and joints can be painful and lead to serious damage.
Individuals can be treated with intravenous injections of the missing protein.

25. Hemophilia XHXh XHY Hh x HH XH XHXh XH Y Xh XHXH XHXH XHY XHY XH Xh XH
sex-linked recessive
Hemophilia
XHXh
XHY
Hh x HH XH
XHXh XH Y
male / sperm Xh
XHXH
XHXH
XHY
XHY XH Xh
female / eggs XH
XHY
XHXh
XHXh
XhY
XhY Y
carrier
disease

26. X-inactivation Female mammals inherit 2 X chromosomes XH XHXh Xh
one X becomes inactivated during embryonic development
condenses into compact object = Barr body
which X becomes Barr body is random
patchwork trait = “mosaic”
patches of black
XH
XHXh
Xh
tricolor cats can only be female
patches of orange

27. Male pattern baldness Sex influenced trait
autosomal trait influenced by sex hormones
age effect as well = onset after 30 years old
dominant in males & recessive in females
B_ = bald in males; bb = bald in females

28. PENETRANCE
the frequency of expression of an allele when it is present in the genotype of the organism (if 9/10 of individuals carrying an allele express the trait, the trait is said to be 90% penetrant)

29. EXPRESSIVITY
the range of signs and symptoms that can occur in different organisms with the same genetic condition.
For example, the features of
Marfan syndrome vary widely—
some people have only mild
symptoms (such as being
tall and thin with long, slender fingers), while others also experience life-threatening complications involving the
heart and blood vessels.

30. Environmental effects
Phenotype is controlled by both environment & genes
Human skin color is influenced by both genetics & environmental conditions
Coat color in arctic fox influenced by heat sensitive alleles
The relative importance of genes & the environment in influencing human characteristics is a very old & hotly contested debate
a single tree has leaves that vary in size, shape & color, depending on exposure to wind & sun
for humans, nutrition influences height, exercise alters build, sun-tanning darkens the skin, and experience improves performance on intelligence tests
even identical twins — genetic equals — accumulate phenotypic differences as a result of their unique experiences
Color of Hydrangea flowers is influenced by soil pH

31. CHROMOSOMAL MUTATIONS

32. Triploid: 3n (endosperm in angiosperm seeds)
Polyploid: >2n (common in plants, found in 1 species of mammal-the viscacha rat!)

33. NONDISJUNCTION

34. Karyotype
Aneuploidy
Trisomy

35. Down syndrome
Trisomy 21
In most cases, Down syndrome occurs when there is an extra copy of chromosome 21. This form of Down syndrome is called Trisomy 21. The extra chromosome causes problems with the way the body and brain develop.

36. Turner’s syndrome
In Turner syndrome, cells are missing all or part of an X chromosome. The condition only occurs in females. Most commonly, the female patient
has only one X chromosome.
Others may have two X
chromosomes, but one of
them is incomplete.
Sometimes, a female has some
cells with two X chromosomes,
but other cells have only one.

37. Klinefelter’s syndrome
Males who have Klinefelter syndrome have an extra X chromosome (XXY), giving them a total of 47 instead of the normal 46 chromosomes. They are sterile.

38. Fragile X syndrome
Results in mental retardation
More likely to occur in a female’s X chromosome
More often observed in males because they inherit their X chromosome from their mothers

39. Phenylketonuria (PKU)
Phenylketonuria (PKU) is a rare condition in which a baby is born without the ability to properly break down an amino acid called phenylalanine.
It is an autosomal recessive trait
Treatment involves a diet that is extremely low in phenylalanine, particularly when the child is growing.

40. Cystic Fibrosis
Cystic fibrosis is a disease passed down through families that causes thick, sticky mucus to build up in the lungs, digestive tract, and other areas of the body.
An estimated 1 in 29 Caucasian Americans have the CF gene.
It is an autosomal recessive trait

41. Huntington’s disease
Nerve cells in certain parts of the brain waste away, or degenerate.
Caused by a genetic defect on chromosome 4. The defect causes a part of DNA, called a CAG repeat, to occur many more times than it is supposed to.
As the gene is passed down through families, the number of repeats tend to get larger. The larger the number of repeats, the greater your chance of developing symptoms at an earlier age. Therefore, as the disease is passed along in families, symptoms develop at younger and younger ages.
It is an autosomal dominant trait
UC Irvine's Leslie Thompson is one of the world's
leading Huntington disease researchers.

42. Tay-Sachs disease
The body lacks hexosaminidase A, a protein that helps break down a chemical found in nerve tissue called gangliosides. Without this protein, angliosides, particularly ganglioside GM2, build up in cells, especially nerve cells in the brain. Symptoms usually appear when the child is 3 to 6 months old. The disease tends to get worse very quickly, and the child usually dies by age 4 or 5.

43. GENOMIC IMPRINTING
Certain genes are imprinted depending on whether they belong to a maternal or paternal chromosome
Prader-Willi syndrome
Deletion of part of chromosome 15 from father
Angelman syndrome
Deletion of part of chromosome 15 from mother

44. Extranuclear genes
Genes are also found in mitochondria and plastids (eg. Chloroplast)
These genes do not display Mendelian inheritance
Mitochondria are always inherited maternally

45. LINKED GENES

46. Any Questions?