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
WW = white flowers
RW = pink flowers
make 50% less color RR Rr rr

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

5. Incomplete dominance CRCW x CRCW CRCR CR CW CRCW CRCR CRCW CR CW CRCW%
genotype %
phenotype
CRCR
25%
25% CR CW
male / sperm
50%
50%
CRCW
CRCR
CRCW CR CW
female / eggs
CRCW
CWCW
CRCW
CWCW
25%
25%
1:2:1
1:2:1

6. Incomplete Dominance Example
Morning glories show incomplete dominance. Purple flowers come from crossing blue-flowered and red-flowered plants. How can I get the most purple-flowered plants?
1st – Find letters!
2nd – Work backwards!

7. Example Cont’d CB CB CR CRCB CRCB CR CRCB CRCB
Crossing a homozygous red-flowered plant with a homomzygous blue-flowered plant would yield the most purple flowered plants. CR
CRCB
CRCB

8. Codominance - Blood Types
2 alleles affect the phenotype equally & separately
not blended phenotype
example: ABO blood groups
3 alleles (multipl alleles)
IA, IB, i
IA & IB alleles are co-dominant to each other
both antigens are produced
both IA & IB are dominant to i allele
produces markers on the surface of red blood cells

9. Multiple Alleles - Blood Types
Multiple Alleles – 3 or more kinds of alleles per gene spot.
Blood types are codominant AND have multiple alleles
B = gene for Blood type.
It has three alleles: A, B, and O
H = gene for Height.
It has two allele forms, T and t H H B B

10. 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

11. Blood compatibility 1901 | 1930 Matching compatible blood groups
critical for blood transfusions
A person produces antibodies against antigens in foreign blood
wrong blood type
donor’s blood has A or B antigen that is foreign to recipient
antibodies in recipient’s blood bind to foreign molecules
cause donated blood cells to clump together
can kill the recipient
Karl Landsteiner
( )

12. Blood donation clotting clotting clotting clotting clotting clotting

13. Blood Type Example 1:
Mom is Type A. Dad is Type O. What are the blood type possibilities for the kids?

14. Blood Type Example 1 Cont’d
Mom’s possible genotypes: IAIA or IAi
Dad’s genotype: ii i IA
IAi ii i IA
IAi

15. Blood Type Example 2
Mom is Type A and the child is Type B. She says Burt is the father. Burt has Type O blood. Is he the baby’s father?

16. Blood Type Example 2 Cont’d
Mom is IAIA or IAi
Burt is ii
Baby is IBIB or IBi
NOT possible, as the baby could not have gotten an IB allele from either of these two people.
Blood typing: Determining if a child is NOT the offspring of two parents.

17. Codominance - Sickle Cell
Sickle cell anemia is another example of codominance in humans.
No sickle cell anemia (homozygous normal) = HNHN
All blood cells are normal in shape
Sickle cell anemia (homozygous abnormal) = HSHS
Blood cells are sickle shaped
Heterozygous individuals (HNHS) can still experience health problems, as BOTH the normal and abnormal alleles are codominant.

18. Sickle-Cell Anemia Cont.
The life space of the sickle-shaped blood cells are shorter than that of normal blood cells.
A lower number of red blood cells causes the patient to also suffer from Anemia.

19. A note on dominance Because an allele is dominant does not mean…
it is better, or
it is more common
Polydactyly
dominant allele

20. Polydactyly recessive allele far more common than dominant
individuals are born with extra fingers or toes
the allele for >5 fingers/toes is DOMINANT & the allele for 5 digits is recessive
recessive allele far more common than dominant
 only 1 individual out of 500
has more than 5 fingers/toes
 so 499 out of 500 people are homozygous recessive (aa)

21. Pleiotropy Most genes are pleiotropic
one gene affects more than one phenotypic character
wide-ranging effects due to a single gene
dwarfism (achondroplasia)
gigantism (acromegaly)
The genes that we have covered so far affect only one phenotypic character, but most genes are pleiotropic

22. Acromegaly: André the Giant

23. 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
eye color
intelligence
behaviors

24. 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

25. Classes of chromosomes
autosomal chromosomes
sex chromosomes

26. Discovery of sex linkage
true-breeding
red-eye female
true-breeding
white-eye male X P
100%
red eye offspring F1
generation
(hybrids)
100%
red-eye female
50% red-eye male
50% white eye male F2
generation

27. 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

28. 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

29. What’s up with 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

30. Genes on sex chromosomes
Y chromosome
few genes other than gender determinant
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
Male-pattern baldness
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.

31. 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

32. 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”
XH
XHXh
Xh

33. X-inactivation & tortoise shell cat
2 different cell lines in cat

34. Map of Human Y chromosome?
< 30 genes on Y chromosome
Sex-determining Region Y (SRY)
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)
Air guitar (RIF)
Scratching (ITCH-E)
linked
Spitting (P2E)
Inability to express affection over phone (ME-2)
Selective hearing loss (HUH)
Total lack of recall for dates (OOPS)

35. Sex-linked traits summary
follow the X chromosomes
males get their X from their mother
trait is never passed from father to son
Y-linked
very few genes / traits
trait is only passed from father to son
females cannot inherit trait

38. 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.

39. Sex Linked Example: Hemophilia
Hemophilia is recessive to normal blood clotting and sex-linked.
Letters?
Normal = N
Hemophilia = n
What are the chances of having a child with hemophilia if Dad is normal and mom is a carrier?
Carriers are individuals that carry an allele for the disease, but usually do not have the disease themselves

40. Hemophilia XNXn XNY Hh x HH XN XNXn XN Y Xn XHXH XNXN XNY XHY XN Xn XN
Hemophilia is
sex-linked recessive
Hemophilia
XNXn
XNY
Hh x HH XN
XNXn XN Y
male / sperm Xn
XHXH
XNXN
XNY
XHY XN Xn
female / eggs XN
XNY
XHXh
XNXn
XhY
XnY Y
carrier
disease

41. is sex-linked & recessive
Male pattern baldness
Sex influenced trait
autosomal trait influenced by sex hormones
age effect as well = onset after 30 years old
Letters?
Normal = N
Bald = n
Male Pattern baldness
is sex-linked & recessive

42. Sex Linked Example: Baldness
Regular Hair is normal and sex-linked. Cross carrier (heterozygous) female with normal male.
Letters?
Normal = N
Bald = n
Parents?
XNXn x XNY
Remember, for baldness the Y chromosome NEVER has a sex-linked gene!

43. Sex Linked Example Cont’d
Cross: XNXn x XNY
Genotypes: 1 XNXN, 1 XNXn, 1 XNY, 1 XnY
Phenotypes: 1 Female, Normal
1 Female carrier
1 Male, Normal
1 Male, bald
Males only need one recessive to have the condition! XN Y XN
XNXN
XNY
XNXn
XnY Xn