Polygenic inheritance

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：
程
晓
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 Segment 1
quantitative trait

Segment 2
hypothesis of polygenic
inheritance
character of polygenic
inheritance
作
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：
程
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Segment 3
polygenic disease
1 、 liability and
threshold
2 、 hereditabilit
y
3 、 the characteristic
of Polygenic
4 、disease
the recurrence risk
forPolygenic 作
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disease ：
程
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Basic concept
Polygenic inheritance: generally, this implies the
disease is the result of additive of multiples of different
genes, each of which, acting alone, would be insufficient to
cause the disease. Each of the contributory genes may
have an equal weight; some may have major effects in
conferring risk for the disease, whereas others might weigh
in with relatively minor contuibutions.
Polygeni Multiples Additive
c of effect
disease different
genes
Environmental Additive
作
etiologies gene 者
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Complex 程
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inheritance 丽
Segment
1Quantitative
traits of
polygenic
inheritance
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What is the difference
between qualitative trait
and quantitative trait

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Example 1
Pattern of
inheritance? Complete
syndactyly AD dominan
ce
The The
affecte normal
Controled by
d
discontinuous
distinguishable
AA/Aa aa 作
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2~3 groups ：
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 Human
Example 3 heigh
numbe
r Controled by
70
60 continuous
50
40 Undistinguisha
30 ble
20 Normal
distribution
10
145 155 165 175 185
150 160 170 180
Height 作
cm 者
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Distribution of people’s 程
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height 丽
Segment
2
Polygene
hypothesis and
its genetic
character
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程
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 polygene hypothesis

1. Quantitative trait is result of multiple

pairs of genes.

2. The relationship of different pairs of genes

are neither dominance nor recessive ， to the
contrary, co-dominant.

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3.Each gene play a minor role in
causing the disease or trait.we call
them minor gene.but their can make
a combined impact and produce an
obvious phenotype. We call this
phenomenon as additive effect,and
call each gene as additive gene.
4. Formation of quantitative trait is
affected not only by additive
genes,but environmental
factors(nutrition, breed, rate of
growth, and amount of
exercise,education,etc) 作
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What is the characteristic
of polygenic inheritance

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：
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the characteristic of polygenic inheritance

1. Mating of two homozygotes will produce offspring of

intermediate phenotype. But with affection of
environment, variation will appear in a certain range.
2. If two heterozygotes mate, most of their children are of
intermediate phenotype. But with gene’segration and
recombination, and with affection of environment,
more variation will appear in a extensive range. And
the extreme variation individuals can be observed.
3. In a population of randomly mating, variation range is
abroad, but most individuals are around of
intermediate phenotype ， individuals of extreme 作
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variation are rare 。 ：
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Example fathe mother
1 r
AaB
gamete b

AB Ab aB ab
AABB AABb AaBB AaBb
AB 9 kinds
of
AABb AAbb AaBb Aabb genotype
Ab s

AaBB AaBb aaBB aaBb

aB 5 grades
作
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AaBb Aabb aaBb aabb ：
ab 程
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Example 2 height
hypothesis: height is determined
by three pairs of unlinked
alleles.Among these genes,A1B1C1
can contribute much more than
A2B2C2. AB1 1
A1B1 A2B2 C1A2
C1A1 C2A2 B2C2
B1C1 B2C2
F1

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 heigh
Example 2
t
8 kinds of gametes

27 genotypes

F2
A1B1 7 grades
C1A2
B2C2 作
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The variation of height of F2

2
0
1 1
5 5
6 6
1 1
1152 3132 5112
0162 2142 4122 6102
作
The recombination of 者
：
genes 程
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Segment 3
Polygenic
disease
1 、 the liability and
threshold
2 、 calculate the
hereditability
3 、 hereditary character
of polygenic disease

4 、 evaluate the risk of 作

者
：
polygenic disease 程
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 1 、 liability
liability the probability of developing some
kind of polygenic disease which is due to both
multiple genes and environmental factors.
In population ,variations of individual’s liability present
bell- shaped curve. Namely, most individual’s liability
approach average value.
Number of individuals

threshold
average

incidence 作
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程
low variations liability high 晓
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 high The risk is
high
liability

low The risk is low

Extreme
Populatio
Normal
n’s
distribution
liability
intermedia 作
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te ：
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Threshold: the value of liability above which
individuals will develop disease.

In certain environment, threshold means the

minimum number of disease genes contribute
to certain polygenic disease.

20
T
15 易
患
10 性
平
5 均 incidence
值
作
Low high 者
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liability 程
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 The number of disease gene required
meaning
Devide the general population into two groups
How to calculate the
liability

Can you calculate the individual’s liability

directly ？
The individual’s liability only can be estimated on
the grounds of the risk of his(her) children
How to evaluate the average of liability of a
population ?
According to the incidence of the population 作
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Basic concept 68%

16%
100%

99.74%
95.4
%

0. 1 3% 2.3%作
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 T
group 1
0.13%

low liability high

group 2
2.3%

作
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The distance between the average and T 程
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Heritability and it’s
calculation

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 Basic concept
heritability, H or h 2
The proportion of the aetiology that can be
ascribed to genetic factors as opposed to
environmental factors （ Degree to which a
given trait is controlled by inheritance ）

Genetic factors Environmental

factors
h2 ＞ h2 ＜
40%
作
70% 者
：
high low 程
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Calculate the heritability
1. by the incidence of general
population and patients’
relatives respectively

h2 = b / r
h 2 : heritability
r : coefficient of kinship

b : coefficient of regression 作
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：
程
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 population
T
b =(Xg – Xr)/a
X g :average liability minus T Xg

X r :average liability minus a

T

a :average liability minus Xr

average liability
作
relatives 者
All items can be get from the ：
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table 晓
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 Congenital
Example 1 atrium
100 families default
total patients incidence q X a
general — — 0.001 3.090 3.367
relative 669 22 0.033 1.838 --
b =(X g – X r )/a
=(3.090 –1.838)/3.367
=0.372
h2 = b / r 作
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：
= 0.372 / 0.5 = 74.4% 程
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 Example 2 胃溃疡
total patients incidence q X a
general — — 0.04 1.751 2.154
relative 0.08 1.405 --

b =(X g – X r )/a
=(1.751 –1.405)/2.154
=0.162
h = b / r
2 作
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：
= 0.162 / 0.5 = 32.4% 程
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2. by the incidence of patients’
relatives and controls
respectively
b =p c (X c – X r )/a c p c =1- q
X c :average liability minus
T
X r :average liability minus
T

a :average liability minus average liability

q:incidence of relatives of 作
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control ：
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 Renal
Example calculus
Considering the control’ age, gender
total patient incidence q pc(1-q) X a
control 1473 6 0.00407 0.99593 2.652
2.962
patient 1437 36 0.02505 -- 1.960 --
b =p c (X c – X r )/a c
= 0.99593 (2.652 – 1.960)/
2.962
=0.233
作
h2 = b / r 者
：
程
= 0.233 / 0.5= 46.6% 晓
丽
3.by concordance of MZ and DZ

H =(C MZT － C DZT ) / (100 － C DZT )

C MZT : concordance of MZ
C DZT : concordance of DZ

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 Examples
concordance= the number of twin with
same phenotype/the total number of
twins ×100
H =(C MZT － C DZT ) / (100 － C DZT )
schizophrenia

h 2 = ( 80% － 13% ) ／ ( 1 －
13%=77%)
diabetes mellitus
作
h = （ 83% － 37% ）／ (1 －
2 者
：
37% ）
=73%
程
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The characteristic of the
polygenic diseases
1. no mendelian pattern of
inheritance
1/2 or ¼ ?
2. familial aggregation

3. risk 作
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The incidence of the general, the first, second,
third degree relatives of the patients
T

G 3 2 1 作
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The highest incidence 程
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 4. The risk is influenced by
consanguineous marriage, but not
strongly as the AR

5. Incidence vary from ethnic

Incidence
disease Chines Japanes America
e e n
Cleft spine 0.003 0.003 0.002
Anencephalia 0.005 0.006 0.005
cleft lip ± palate 0.0017 0.003 0.0018
作
Congenital talipes 0.008 0.014 0.055 者
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 Recurrence risks
1. Empirical formula
Incidence Incidence of
of heritability relatives of
population first degree
当 P = 0.1% h 2 = 70% F =√P
～ 1% ～ 80%

当 >1.0% > 80% F >√P

当 < 0.1% < 70% F <√P

2. The more members in a family, 作
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the high risk of the relatives 程
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3.the more severe,the higher risk of the
relative

exampl severity Recurrence

e risk
Unilateral cleft lip 2.6%
cleft lip ± palate
U cleft lip ± palate 4.21%
bilateral± palate 5.6%
4. When incidence are different
between different gender..

High Low in
incidence children 作
Low High in 者
：

incidence children
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 Congential
0.5 pyloric stenosis
%
0.1
%
General
population 5.5
%
2.4
%
Relatives
20%
of male
7.3 patient
%
作
Relatives of 者
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female patient 程
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 key point
1.the difference between the
qualitative trait and
quantitative trait
2.the polygenic hypothesis
3.liability, threshold,
heritability
4.the characteristic and the
recurrence of polygenic
inheritance
5.how to calculate the
heritability
作
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程
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Cleft spine
cleft lip ± cleft palate
Anencephalia
Congenital talipes