Fudan University, the latest Cell of the Chinese Academy of Sciences: For the first time, the association between fingerprints and physical development genes is revealed

In the early morning of January 7, the team of researcher Wang Sijia of Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, the team of Professor Denis Headon of the University of Edinburgh, and the team of Professor Jin Li, academician of the Chinese Academy of Sciences, president of Fudan University, and dean of the Institute of Human Phenotyping, joined more than ten scientific research institutions at home and abroad.
Published the paper " Limb development genes underlie variation in human fingerprint patterns " in the top international journal "Cell " .

After 7 years, the research results for the first time found that the genes related to fingerprints were significantly enriched in the pathways related to limb development and formation rather than the pathways related to skin development.

The paper will be officially published in the first issue of Cell in 2022
.

How did such a pioneering achievement come about? How to subvert the previous perception of fingerprint patterns? What is the relationship between skin lines and human health? What value will be generated in the future? Scan your fingerprint and let's unlock curiosity-driven research together
.

First discovery: The key role of limb development genes in the formation of fingerprint patterns

Fingerprints, as a type of skin pattern, exist before we are born, and are formed in the early embryonic development, starting from the 3rd to 4th month of pregnancy, and ending with the exposure of the epidermal ridge line in the 6th month
.

In existing studies, some scholars have suggested that the formation of skin lines may be affected by the stimulation of basal cell folding, the involvement of growth forces such as bones, and the symbiosis of blood vessels and nerves
.

From the data of twins, the fingerprint phenotype has a certain degree of heritability, "but which genes are regulated and influenced behind it? How much does it contribute to the fingerprint pattern? How does it work? These questions were all before this study.

To truly crack the mystery of the formation mechanism of fingerprint patterns, a large number of samples and data are needed
.

Zhang Haiguo at the skin pattern collection site

But as the sample size increased, interesting results emerged
.

In the 1920s and 1930s, some scholars observed that the fingerprint patterns on different fingers were similar
.

Until 2005, scholar AS Nagy named the similarity of fingerprint patterns on each finger as "pattern influence", that is, the fingerprint patterns between the middle three fingers (left and right index finger, middle finger, ring finger) are highly correlated
.
Decades have passed, and no one knows what the mechanism is behind it
.

"It is difficult and inefficient to find a gene that affects a single phenotype.
The biggest breakthrough of this research is the phenotypic integration, which integrates the fingerprint patterns of a single finger to form a composite phenotype, which is larger than previous studies.
Then we found that they strongly point to the same signal
.
" Li Jinxi said
.

The team found that a variant site adjacent to the EVI1 gene in the 3q26.
2 region was significantly associated with the composite phenotype of the fingerprints of the middle three fingers
.
Therefore, it also provides a phenotypic and genetic explanation for the "pattern influence" proposed by the predecessors, that is, the "pattern block" mentioned in this study
.

In the next collaboration with the research team of the University of Edinburgh, Chinese and foreign scientists observed through mouse animal models that EVI1 changes the skin pattern of mice by regulating limb development rather than skin development
.
The same phenomenon has also been observed in human embryonic tissue
.
The team found that EVI1 is mainly expressed in mesenchymal cells during limb development, rather than epithelial cells during skin development, supporting its role in shaping limbs and fingers during human fetal tissue from limb development to dermal striae formation
.
This further shows that fingerprint-related genes affect the formation of fingerprint patterns by regulating limb development, rather than regulating skin development by traditional cognition
.

In order to gain a more comprehensive understanding of the genetic structure of fingerprint patterns, the team also sought out partners in the United States, the United Kingdom, and Australia to conduct a large-scale meta-analysis of more than 23,000 individuals in existing cohorts of East Asian ancestry and European ancestry worldwide.
, analyzed millions of genetic loci and identified 43 genetic loci and 105 significant genes associated with human fingerprint patterns
.

To further test the hypothesis that embryonic and fetal limb development may affect fingerprint pattern patterns, the team also tested the correlation between fingerprint patterns and limb-related phenotypes (i.
e.
, watch patterns) and found that fingerprint patterns were broadly correlated with finger length ratios.
and have a common genetic basis
.
For example, the longer the little finger and the shorter the palm, the more the double-handed pattern; and the longer the distal phalanx of the index finger (where the fingerprint is formed), the less the bucket-shaped pattern
.

It is a kind of courage to bravely enter the "no man's land" in scientific research, and it is also a kind of innovation ability
.
Jin Li made a vivid analogy, "Without innovative sources, especially original ones, scientific research is like picking fruit from someone else's tree, and it is difficult to get rid of the role of running behind and the dilemma of being 'stuck in the neck'.

In order to achieve the lead and not be 'stuck in the neck', fundamentally, we must plant our own original innovation trees in various disciplines and pick the scientific fruits from our own trees
.
"

Wang Sijia said bluntly: "This is a research driven by curiosity
.
We don't know what the results will be
.
" But for scientific research, "Curiosity is the most precious thing, especially basic research, or it is utilitarian.
, do something interesting, and after doing it, maybe there will be some unexpected discoveries
.
"

The significant scientific significance of the results is:

Provide an important theoretical basis for the study of the association between phenotype and disease, and help to draw the next-generation "navigation map" of life science research

"This study provides a classic case for the study of human phenotypes, which fully demonstrates the great significance of human phenotypes to the future development of life sciences
.
" Jin Li said about the scientific significance and value of this research
.

He introduced, "Through research, we have found for the first time that there is a strong correlation between fingerprint patterns and limb phenotype, and the mechanism behind the strong correlation is that the formation of fingerprint patterns and the development of limbs are affected by the same gene - EVI1
.
It embodies the typical "one-cause pleiotropic effect" in biology, and the "one-cause" here is the gene for limb development
.
"

Based on the results published this time, in the direction of fingerprint pattern research in the future, scientists may be able to further discover that some fingerprint-related phenotypes that were previously thought to be less related to health and disease are actually related to certain diseases.
In this way, it can provide useful information for the general public to predict health risks in advance, detect and intervene in advance
.

Wang Sijia introduced the research results

What is "one cause with multiple effects"? Wang Sijia explained: "There is a common cause behind seemingly unrelated phenotypes.
In this study, skin lines, finger length, etc.
are all related to genes related to limb development
.
In real life, a typical example is drinking.
Association between blushing and susceptibility to cardiovascular disease
.
"

The "one cause with multiple effects" revealed by this study provides an important theoretical basis for the study of the association between skin lines and other human phenotypes and diseases, and is expected to open up the connection and mechanism of macro and micro phenotypes
.
"For example, the scientific community has discovered the association between different dermatoglyphic phenotypes and many congenital genetic diseases, such as patients with Down syndrome may have features such as amputated palms and arched balls of the great toes
.
" Wang Sijia introduced
.
In the future, the team will focus on more neglected and seemingly "useless" phenotypes for more research
.

The so-called "phenotype", simply put, is the various characteristics of living organisms, which are the result of the combined action of genes and the environment
.
For example, whether a person has single eyelid or double eyelid, the depth of skin color, whether it is easy to blush when drinking, whether the earlobe is wrinkled,
etc.
Common physiological, biochemical, and metabolic indicators such as cholesterol, blood lipids, and blood pressure, as well as functional indicators such as speed and strength, are all phenotypes
.

The human phenotype is holistic and systematic, and to decipher the association mechanism between macro-micro phenotypes, it is necessary to collect phenotypic data as many, complete and continuous as possible from a fairly large group of volunteers, that is, " Measure everything is measurable" scientific research guiding ideology
.

With the support of the first batch of municipal-level major projects in Shanghai, Fudan University, in conjunction with domestic and foreign partners such as the Chinese Academy of Sciences, has taken the lead in promoting the "Human Phenotype Group" big scientific project on a global scale.
The strong correlation between phenotypes, especially the strong correlation between phenotypes that have not been noticed by scientists and are closely related to human health, draw a "navigation map" composed of various strong correlations for future life.
Health research provides new guidance and direction
.

"This research result is an exemplary achievement achieved by Fudan, the Chinese Academy of Sciences and other parties taking the lead in promoting the 'Human Phenotype Group' large scientific plan with the strong support of Shanghai,
" said Jin Li
.

It is gratifying that, with the joint efforts of Chinese scientists, based on the cohort study of more than 800 natural populations carried out by Fudan University, each person measured nearly 30,000 phenotypes, the world's first "human phenotype" has been preliminarily drawn.
Group Navigation Map”, and found more than 1.
5 million strong associations, of which cross-scale strong associations accounted for 39%, and most of them were discovered for the first time in the scientific community
.

This "navigation map" not only brings gratifying signals to the scientific community, but also raises more new "question marks".
It is expected to become an important work guide in the field of life sciences, and needs to be further studied and solved by scientists around the world
.
This is also one of the important next steps of Fudan University
.

From 0 to 1, there is more to do in the future 

In 2005, on the occasion of its 125th anniversary, Science published the "125 Most Challenging Scientific Problems", which has guided the scientific development in the past ten years
.
After 16 years, in 2021, Science will publish the "New 125 Science Questions"
.
One of the questions is: "What genes make us unique?" This study may provide a tiny fraction of the answer
.

"We have only taken a small step in skin pattern research, which is a process from 0 to 1.

Although the previous cognition has been updated theoretically, there are still many gaps
.
Many directions triggered by this step are waiting for Solve the problem
.
" Li Jinxi said
.

Li Jinxi introduced the skin pattern collection process

After the paper was published, the team members did not stop.
"The data in the paper is as of 2019, but our instruments are still sampling everywhere
.
We will first focus on various congenital diseases that may be directly related to genes.

We hope to be able to continuously measure phenotype data for a group of people more, more deeply, and more completely, so as to more systematically and precisely analyze the correlation between mechanical phenotypes
.
” And this is the Shanghai-level science and technology led by Fudan University.
A key part of the work of the major project "International Human Phenotyping Project (Phase I)"
.

"Like we found, EVI1 has many other effects, so is it possible to use this as a link to discover and decipher the association between fingerprint patterns and other phenotypes?" With the collection box, the team set off again
.
Facing the vast "universe" of the human phenotype group, which is full of unsolved mysteries, Li Jinxi is full of excitement and enjoys it
.

There is more to be done in the future
.

Paper link: https://authors.
elsevier.
com/sd/article/S009286742101446X