Human Genome Diversity
Research in China
Chu Jiayou,
Institute of Medical Biology,
Chinese Academy of Medical Sciences,
Kunming 650118
„
There are 56 nationalities in China,
each of them having independent
inhabitation areas. And some of
them are genetic isolated population.
In the source of nationalities and
genetic phenotypes, each nationality
has its unique characteristics. There
are
significant
differences
in
categories,
enzyme
system,HLA
antigen and incidences of some
genetic diseases.
Yi
Jino
Dulong
Lisu
Bai
Achang
Naxi
Hani
Pumi
Tibetan
Lahu
Chinese populations
Nationalities Population .Nationalities Population .Nationalities Population
** Achang
27,708
**Jingpo
119,209
Qiang
198,252
**Bai
1,594,827
**Jino
18,000
Russian
13,504
Baoan
12,212
Kazak
1,111,718
Sala
87,697
**Blang
82,280
Kirgiz
141,549
She
630,378
*Bouye
2,545,059
Korean
1,920,597
*Shui
345,993
**Dai
1,025,128
**Lahu
411,476
Tajik
33,583
Daur
121,357
Lhoba
2,312
Tatar
4,873
**De'ang
15,462
Li
1.110,000
*Tibetan 4,593,330
Dong
2,514,014
**Lisu
574,856
Tu
191,624
Dongxiang
373,872
*Manchu
9,821,180
Tujia
5,704,223
**Dulong
5,816
Maonan
71,968
Uygur
7,214,431
Ewenki
26,315
*Miao
7,398,035
Uzbek
14,502
Gaoshan
400,000
Moinba
7,475
**Wa
351,974
Gelao
437,997
*Mongolian 4,806,849
Xibe
172,847
*Han
1.2 billion
Mulao
159,328
*Yao
2,134,013
**Hani
1,253,952
**Naxi
278,009
*Yi
6,572,173
Hezhe
4,245
**Nu
21,723
Yugur
10,569
*Hui
8,602,978
Oroqen
6,965
*Zhuang
15,489,630
Jing
18,915
**Pumi
29,657
_____________________________________________________________________________________
* and ** distributed in Yunnan province.
** only resided in Yunnan province
Chinese Human Genome Diversity ,As a part of
Chinese Human Genome Project
„
„
Biodiversity is so important, human being
should not forget it’s own diversity.
____ Prof. Min Wu, A
Chinese Human Genome Project
founder of
Why human genome diversity research in China is
focused in Yunnan province.?
„
„
Among 56 nationalities of China,
there
are 26 nationalities with populations of
more than 5000 living together in Yunnan
province. Among 26 nationalities, 15 are
only living in Yunnan province: Bai, Hani,
Dai, Lisu, Lahu, Wa, Naxi, Jingpo, Bulang,
Pumi, Nu, Achang, Deang, Jino and Dulong.
Geographical Distribution of Sino-Tibetan Populations
Geographical Distribution of Sino-Tibetan Populations
Why are so many nationalities in
Yunnan province?
„
„
1 . Specific historic reasons make many
nationalities migrating to Yunnan.
During the 5th century B.C. to 3rd century
B.C.,
Xiongnu people in Mongolian Plain
became stronger gradually and began to
expand its territory to Qinhai and Gansu
province. As a result, two ancient
nationalities of Di and Qiang were expelled
to the southwest China. In addition,
ancient wars made some nationalities
migrate to Yunnan to seek asylum. From
then on, these nationalities settled down in
Yunnan province.
„
„
2 . Complicated geography and climate of
Yunnan.
The complicated geographic environment,
climate and rich natural resources in
Yunnan province just fit for those different
nationalities’ living customs. Therefore,
Yunnan becomes an ideal place for many
nationalities to settle down.
„
„
3 . Yunnan is isolated from outside for a
period of time.
Yunnan province is isolated from outside
because of long-term feudal rule, regional
domination
and
inaccessibility
in
transportation. Furthermore, separating
from
outside,
backward
mode
of
production and lower needs for living made
many
nationalities
keeping
in
a
independent and isolated state.
„
At present, more and more youths
are married each other among
different nationalities, genome of
some nationalities face the danger of
extinction.
Therefore,
the
reservation of different nationalities
genome become an urgent project.
If measures have not been taken
from now on , we will lose the
opportunity forever.
Three focuses of our study
1.
2.
3.
Reservation of different Chinese
populations’ genome (cell bank and
genome DNA bank).
Research on genetic diversity.
Research on relationship between
diversity and disease gene.
Co-operation groups
-Institute of Medical Biology, Chinese
Academy of Medical Sciences,Kunming
-Harbin Medical University,Harbin
-Institute of Genetics, Chinese Academy of
Sciences, Beijing
-Chinese Western Medical College,Chengdu
-Fudan University,Shanghai
Examples of our Current Work 1
„ Sample collection and cell line
Establishment
„
For this study, consulting with nationality
scholars , blood samples of healthy
individuals with no relative tie belong to
different populations were collected
at
ethnic groups’
living areas, and 3
generations are investigated and recalled.
This can guarantee the representative of
samples.
„ More
attentions will be paid to
collect some samples from special
genetic disease cases and cases
with special phenotypes. To sample
large
families
with
specific
characteristics of the ethnic group is
also in the plan.
„
„
„
Based on the principle of “informed
consent”
Giving medical consulting service for
local people
„
„
DNA were extracted from blood
samples and qualified. Meanwhile,
use
EB
virus
transformation
technique to establish the genetic
specific immortalized lymphocyte
lines of different nationalities.
中华民族基因组的保存情况Chinese Different Nationalities’ Gene Bank
Ethnic groups
Sampling place
cell line
DNA Samples
Sala
She
Tu
Naxi
Xunhua County, Qinghai Province
Fuan City, Fujian Province
Huzhu County, Qinghai Province
Lijiang City, Yunnan Province
Jinghong
City,
Xishuangbanna
Autonomous Region & Luxi county,
Dehong, Dai and Jingpo Autonomous
Region, Yunnan Province
Luxi County, Dehong, Dai and Jingpo
Autonomous Region, Yunnan Province
Luxi County, Dehong, Dai and Jingpo
Autonomous Region, Yunnan Province
Lhasa City, Tibet Autonomous Region
Baise County, Guangxi Zhuang Auto
nomous Region
Luxi County, Dehong, Dai and Jingpo
Autonomous Region, Yunnan Province
Baisha County, Hainan Province
Yongning Xiang, Ninglang County, Yunnan
Province
Wangqiao Xiang, Dali, Yunnan Province
Paomaping Xiang, Ninglang County,
Yunnan Province
Shaoguan City, Guangdong Province
Najiaying Town, Tonghai County, Yunnan
Province
71
49
39
36
100
100
100
100
62
100
49
100
55
100
51
100
55
100
45
100
57
100
43
100
61
100
47
100
61
100
50
100
Dai
Jingpo
De’ang
Tibetan
Zhuang
Bulang
Li
Moso
Bai
Yi
Han-GD
Hui
Ethnic groups
Han_SD
Lisu
Nu
Dai-Huayao
Oroqen
Ewenki
Daur
Mongol
Koreans
Hezhen
Man
Xibe
Han-Sichuan
Han_Fujian
Sampling place
Zhouping
County
Shandong
Province
Fugong County, Nujiang, Yunnan
Province
Fugong County, Nujiang, Yunnan
Province
Xinping County, Yunnan Province
Ali river Oroqen Autonomous
County, Nei Mongol Province
Na river County, Heilongjiang
Province
Hongyan Daur Autonomous county,
Nei Mongol Province
Haila’er City, Nei Mongol Province
Yanbian Koreans Autonomous
Region, Jilin Province
Tongjiang County, Heilong jiang
Province
Youyian Man Autonomous county,
Liaoling Province
Chabu’er
Xibe
Autonomous
County, Xinjiang Province
Leyu County, Sichuang Province
Minqing County, Fujian Province
cell line
DNA Samples
61
100
56
100
57
100
5
100
39
120
43
120
58
120
62
120
58
120
18
120
65
120
43
120
51
58
120
120
Ethnic groups
Hui
Kazak
Bouyei
Dong
Qiang
Kirgiz
Han-Hunan
Han-Shanxi
Han-Guangdong
Yi
Miao
Tujia
Han-Zhejiang
Han-Henan
Uygur
Yao
Total
Sampling place
cell line
DNA Samples
63
120
64
120
67
120
50
48
57
100
100
100
59
100
58
100
Tongxin County, Ningxia Hui
Autonomous Region, Xinjiang
Province
Yinin Kazak Autonomous Region
Qiannan
Bouyei
Autonomous
Region, Guizhou Province
Sanjiang County, Guangxi Province
Mao County, Sichuang Province
Wuqia County, Xinjiang Province
Shuangfeng
County,
Hunan
Province
Linyou County, Shanxi Province
Guangning County, Guangdong
Province
Butuo County, Sichuan Province
Songtao County, Guizhou Province
Laifeng County, Hubei Province
Jinyun County, Zhejiang Province
Fangcheng County, Henan Province
YIning City, Xinjiang Province
55
100
49
43
56
59
60
60
100
100
100
100
100
100
Du’an County, Guangxi Province
58
100
2411
4860
Examples of our Current Work 2
Research on genetic diversity
STR
Y Chromosome
mtDNA
SNP
Y Chromosome markers
• SNPs
(Single Nucleotide Polymorphisms)
Mutation rate is low
Trace the ancient events
• Microsatellites (Tandem repeat of 2-5 nt)
Mutation rate is high
Trace the recent events
Estimate the age of MRCAs
Allelic Specific PCR in Multiplex of
Five Y Chromosome SNPs
M 1
2
3
4
5
6
7
8
M89 ( 365bp )
M110 ( 250bp )
M50 ( 219bp)
M7 ( 174bp )
M119 ( 144bp )
Y Chromosome Haplotype Frequency
Distributions in East Asian Populations
Cont ine nt
East Asia
Pop ulatio n
Buryat (1)
Ewenki (2)
Manchurian (3)
Mongolia n(4)
Korean (5)
Japanese (6)
Hui (7)
Tibetan (8)
Jingpo (9)
Tuji a (10)
Yao-Nandan (11)
Yao-Jin xiu (12)
Z huang(13)
Dong (14)
Bulang (15)
Lahu (16)
Yi (17)
She (18)
Atayal (19)
Yami (20)
Paiw an (21)
Ami (22)
Li (23)
Cambodia n (24)
NE. Thai (25)
Malays ia n (26)
Batak (27)
Javanes e (28)
Siz e
4
8
18
24
7
29
20
8
5
10
10
10
29
10
5
5
14
11
24
8
11
6
11
26
20
13
18
11
H1
75
50
17
58
21
10
10
50
20
3.6
20
20
20
H2
H3
H4
25
4.2
11
8.3
28
5
13
20
13
25
30
3.6
7.1
H5
H6
13
22
13
57
21
30
13
28
4.2
20
20
30
3.6
H7
17
10
30
10
3.6
10
H8
25
17 5.6
4.2 4.2
43
10 3.4
20
50
100
20
25
20
10
20
14
43
9.1
21
18
29
27
4.2
7.1
18
4.2
18
5.6
9.1
18
20
3.8
12
5
7.7
5.6
9.1
12
5
7.7
11
27
3.8
5
31
11
9.1
9.1
15
5
15
17
54
25
55
100
27
3.8
5
7.7
22
18
10
5
3.8
5
3.8
10
60
18
3.8
H9 H10 H11 H12 H13 H14 H15 H16 H17
40
25
20
60
20
14
9.1
11
8.3
75
27
3.8
5
23
9.1
55
23
45
7.7
28
18
9.1
12
20
YAP+
‹
YAP+(%)
Han
„
„
„
„
„
„
„
„
„
„
„
Diversity
Han(Guandong)
Han(Shanxi)
Han(North)
Han(Yunnan)
„
„
0
0
0
0
Northern populations
Ewenki
Oraqen
Daur
Man
Uygur
Hui
0
0
0
0
4
8
„
„
„
„
„
„
„
„
„
YAP+(%)
Southern populations
Zhuang
Lahu
Wa
Dai
Tujia
Yao
Yi
Tibeten(Yunnan)
Tibeten(Tibet)
0
0
0
0
2
2
15
39
49
Multiple origins of Tibetan
„
„
The YAP+ is an ancient polymorphism that
originated from Central Asia (Altheide and
Hammer, 1997)
Our previous study on extant East Asian
populations showed that M122C (defining H6, H7
and H8) is predominant in East Asian populations,
especially in Han Chinese (54.1% on average) (Su
et al., 1999) but it is nearly absent in other world
populations, including Central Asians (RS Wells,
personal communication).
„
Based on the fact of presentation with high
frequency of both YAP +(41.3% in Zang
and 44.4% in Khamba) and M122C (>35%),
reflects a genetic source of Tibetan Ychromosomes may have been derived from
two different gene pools, one from Central
Asia and the other from East Asia
SNP（Single Nuleotide
Polymorphisms）
• SNP application
– Linkage analysis
– Association study
– Population genetics
– Evolution
– Complex disease study
– Pharmacogenomics
– Individual medical
The 126 genes of 21 chromosome were sequenced
1
ABCG1
45
D SCR5
89
PKNOX1
112
T FF3
2
A D A M T S1
24
CBS
68
K CN J15
113
T IA M 1
3
A D A M T S5
25
CCT 8
69
K CN J6
114
T M EM 1
4
A D A RB1
26
CH A F 1B
70
K IA A 0179
115
T M P RSS2
5
A IRE
27
CLD N 14
71
K IA A 0184
116
T PT E
6
APP
28
CLD N 17
72
K IA A 0539
117
T RP C7
7
AT P 50
29
CLD N 8
73
K IA A 0653
118
T SG A 2
8
AT P 5A
30
CO L18A 1
74
K IA A 0958
119
T T C3
9
B3G A LT 5
31
CO L6A 1
75
K IA A O 136
120
U 2A F 1
10
BA CE2
32
CO L6A 2
76
LSS
121
U BE2G 2
11
BA CH 1
33
CRYA A
77
M CM 3
122
U SP 16
12
BT G 3
34
CRYZ L1
78
M X1
123
U SP 25
13
C21orf1
35
CST B
79
M X2
124
WD R4
14
C21orf18
36
CT BP 2
80
N 143
125
WD R9
15
C21orf2
37
CX A D R
81
N CA M 2
126
WRB
16
C21orf258
38
D 21S2056E
82
N D U F V3
17
C21orf30
39
D N M T 3L
83
N RIP 1
18
C21orf33
40
D SCA M
84
P CN T
19
C21orf4
41
D SCR1
85
P CP 4
20
c21orf5
42
D SCR2
86
P D E9A
21
C21orf6
43
D SCR3
87
PDXK
22
CBR1
44
D SCR4
88
PFKL
23
CBR3
67
K CN E2
111
T FF2
The individual samples
No1.
A01
A02
A03
A04
A05
A06
A07
A08
A09
A10
A11
A12
B01
B02
B03
B04
B05
B06
B07
B08
B09
B10
B11
B12
C01
C02
C03
C04
C05
C06
C07
C08
property
individual
individual
individual
individual
individual
individual
individual
individual
individual
control(-)
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
individual
No2.
I1
I2
I3
I4
I5
I6
I7
I8
I9
Sample
Sun L
Han F
Liu H
Zhu L
BF28
BF29
Meng S
Huang g
Ni M
National
Han
Han
Han
Han
Han
Han
Zhuang
Zhuang
Zang
Sample locaiton
Shandong
Shandong
Jilin
Haerbin
Shanxi
Shanxi
Guanxi
Guanxi
Tibet
I11
I12
I13
I14
I15
I16
I17
I18
I19
I20
I21
I22
I23
I24
I25
I26
I27
I28
I29
I30
I31
I10
Ni D
Yan Z
Piao Y
Yan D
Liu Z
Huang F
Su Y
Hu R
GSM1
GSM2
SBYi1
SBYi2
XYUR1
XYUR2
Yan J
HGG21
HGG22
He C
SLE4F
SLE4M
SLE4S1
Zhan D
Bulang
Bulang
Caoxian
Dai
Han
Han
Menggu
Menggu
Miao
Miao
Yi
Yi
Weiwuer
Weiwuer
Dai
Han
Han
Han
Han
Han
Han
Zang
Yunnan
Yunnan
Jilin
Yunnan
Fujian
Fujian
Heilongjiang
Heilongjiang
Guizhou
Guizhou
Sichuan
Sichuan
Xinjiang
Xinjiang
Yunnan
Guangdong
Guangdong
Shanghai
Shanghai
Shanghai
Shanghai
Tibet
age
11
9
37
24
22
8
59
18
30
24
43
17
18
14
14
39
28
Sex
M
M
M
M
F
F
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
F
F
F
M
F
M
M
The pooling samples
No1.
C09
C10
C11
C12
property
pool
pool
pool
pool
No2.
P01
P02
P03
P04
D01
D02
D03
D04
D05
D06
D07
D08
D09
D10
D11
D12
D12
pool
pool
pool
pool
pool
pool
pool
pool
pool
pool
pool
pool
pool
P05
P06
P07
P08
P09
P10
P11
P12
P13
P14
P15
P16
P16
Sample
Sample locaiton
sum
Han North
Han,South
High choleserol
Coronary heart
Disease
SLE
Shanxi
Guangdong
Nanjing
39
Diabetes Ⅰ
NIDDM
Hypertension
Control
Hypertension
Hypotension
Graves' disease
Schizophrenia
Schizophrenia
Affrican
European
European
Shanghai
49
43
239
Shanghai
Shanghai
Beijing
Shanghai
Shanghai
Henan
Henan
Liaoning
Shanghai
Beijing
84
75
96
96
96
36
36
96
200
200
Sex
Examples of our Current Work 3
„ Genetic
analysis of Minority
population in China and its
implication in the origin of
Modern human in the East
Asia.
Three Hypotheses on Modern Human Origin
Time (millions of years)
2.0
Homo erectus
1.5
1.0
0.5
0.0
Homo sapiens
H. s. sapiens
Africa Europe Asia
Australia
Africa
Europe Asia
Australia Africa Europe Asia
Australia
The Formation Of Modern Chinese Populations
from microsatelletes evidence
„
Research materials
28 Chinese populations
„
15 foreign groups as control
Basic methods
Microsatelates
„ Genotyping and Genescan
„ Neighbor-joining method
„
„
What is the difference from the
past researchers?
1.Strict in samples collecting
„ 2.Marks and analysis methods
with
foreign
„ 3.Compared
samples
„
Sea of
Okhotsk
1
2
MONGOLI A
3
4
5North Korea Sea of
U.S. S.R.
Japan
7
CHINA
8
AFGHANI STAN
South Korea
JAP AN
IRAN
NEPAL
PAKISTAN
BHUTAN
INDIA
Gulf of
Oman
BANGLADES H
10
17
11
9
15
12 14
13
16 VI ETNAM
BURMA
Arabi an
Sea
LAOS
25
24
KAMP UCHEA
Andaman
Sea
SRI LANKA
TAIWAN
South
China
Sea
Pacific
Ocean
East
China
Sea 19
18
HONG KONG
23
THAI LAND
Bay of
Beng al
6
20
21
22lippi ne
Phi
Sea
THE
PHILI PPI NE S
Gulf
of Thail and
BRUNEI
MALAY SI A
26
MALAY SI A
SI NGAPORE
27
Indi an Ocean
28
PAPUA
NEW GUINEA
INDONES IA
Coral S ea
AUS TRALIA
11
Main conclusions:
1.There are some genetic
differences between
nationalities in north and
„ south China, but the relations
are quite complicated.
„
Main conclusions:
„
2 . Chinese people’s migration
might be from the south to the
north.
Main conclusions:
„
3.Modern humans originating in
Africa constitute the majority of
the current gene pool in East
Asia.
Sea of
Okhotsk
MONGOLIA
U.S.S.R.
Sea of
North Korea
Japan
CHINA
South Korea
JAPAN
AFGHANISTAN
IRAN
Ocean
East
NEPAL
PAKISTAN
INDIA
Gulf of
China
BHUTAN
Sea
BANGLADESH
Oman
TAIWAN
VIETNAM
BURMA LAOS
HONG KONG
THAILAND
Bay of
Bengal
Philippine
Sea
South
Arabian
Sea
Pacific
China
THE
PHILIPPINES
Sea
KAMPUCHEA
Andaman
Sea
SRI LANKA
Indian Ocean
Gulf
of Thailand
BRUNEI
MALAYSIA
MALAYSIA
SINGAPORE
PAPUA
NEW GUINEA
INDONESIA
Coral Sea
AUSTRALIA
The Formation Of Modern Chinese Populations
From Y chromosomes Evidence.
„
To test the hypotheses of modern human
origin in East Asia, Yuehai Ke and Li Jin(6)
sampled 12,127 male individuals from 163
populations across Southeast Asia,
Oceania, East Asia, Siberia, and Central
Asia and typed for three Y chromosome
biallelic markers (YAP, M89, and M130)
Study on 12,000 Y Chromosomes
„
„
All the individuals carried a mutation coalesce to
another mutation(M168T),which originated in
Africa about 35,000 to 89,000 yeas ago.
Therefore,the data do not support even a minimal
in situ hominid contribution in the origin of
anatomically modern humans in East Asia.
Conclusion
The phylogeny based on microsatellites
and Y chromosomes revealed a clear
distinction between southern and northern
Chinese populations. In both phylogenies
with different loci and populations,
populations from East Asia always derived
from a single lineage indicating the single
origin of those populations.
The current analysis suggests that the
southern populations in East Asia may be
derived from the populations in Southeast
Asia that originally migrated from Africa
and the northern populations were under
strong genetic influence from Altaic
populations from the north.
It is now
probably safe to conclude that modern
human originated in Africa constitutes
majority of the current gene pool in East
Asia .
Examples of our Current Work 4
GENOME DIVERSITY AND DISEASE
Human Origins/Evolution
Disease susceptibility
“Disease is Part of an
Evolutionary Process”
Genome diversity research
related to diseases
G6PD (glucose-6-phosphate dehydrogenase)
Deficiency gene rate
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Dai
Lahu
Deang
Wa
Jingpo
Hani
0.1610
0.1136
0.2014
0.0821
0.0450
0.0370
Incidence rate of abnormal
hemoglobin
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Achang
Jino
Deang
Jingpo
Dai
Lisu
Aini
Bai
Lahu
Hani
Wa
0.4293
0.1625
0.1399
0.1225
0.1212
0.1044
0.1180
0.0479
0.0299
0.0182
0.0182
System lupus erythmatosus is an autoimmune disease,
and a complex polygenic disorder
Problems for complex traits:
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Incomplete penetrance
Phenocopy
Genetic heterogeneity
Polygenic inheritance
High frequency of mutant alleles
Mitochondrial inheritance
Anticipation from trinucleotide repeats
Imprinting
Some conclusions of SLE
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TNFa1(p=0.0281),
TNFc2(p=0.0000)
allele
frequencies were significantly increased in the
SLE group compared to controls.
But
TNFa2
(p=0.0476),
c3(p=0.0043),
c4(p=0.0013), d6(p=0.0448) allele frequencies
were decreased in the SLE group compared to
controls.
Meanwhile, we have found the possible new
genotypes in Yunnan Han population: TNFc3 (size
of
fragment
is
161bp),
TNFc4(163bp),
TNFd7(136bp), TNFd8(138bp), TNFe1(99bp).
Parkinson’s disease
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Parkinson’s disease(PD) is the second most
common neurodegenerative disorder after
Alzheimer’s disease, affecting people seriously.
Although many factors, including circumstance,
neurotoxin etc, are regarded as probable reasons,
genetics analysis in recent years revealed that PD
was associated with some genetic factor.
V1
Linkage mapping analysis of this PD family
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Using 400 microsatellite markers to perform
whole genome genescanning, and position the
rough location of the candidate gene
Design a series of primers to position the exact
location of gene
Detect the mutation of candidate gene and find the
genetic reason of PD
Long-lived people in Bama
Bama in Guangxi province is one of famous
long-lived people counties in the world
„ The fifth Chinese census ( in 2000)
‹ the number of longevous people in Bama
whose age over 100 is up to 74 from 66
in 1990
‹ the proportion of long-lived people,
0.031%, is the highest in the whole world
„
Beautiful Bama
The old people of Bama
Two Pedigrees of Bama Old People
Huang Buhan, male, 105
Huang Mayou, female, 104
Call for international
cooperation
-Data base and analysis
-Compared with foreign samples.
-Exchange DNA samples and cell lines.
-Cooperation on Diversity and Disease Gene
research.
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Acknowledgements
Chinese Natural Science foundation
Ministry of Science and Tecnologe
Chen Zhu, Chinese Academy of Sciences,
Qiang Boqin, Chinese Academy of Medical Sciences
Jin Li, Cincinaty University,USA,
Li Pu , Harbin Medical University ,
Xu Jiujin, Institute of Genetics,CAS,
Huang Wei, Shanghai 2ed Medical University,
Qian Yaping, Chu Zhengtao,Yang Zhaoqing,
Yu Jiankun, Institute of Medical Biology,CAMS