Project description

Our project promotion video for iGEM2020

Our idea

For our iGEM 2020 project we decided to focus on ways we can contribute to prevention of monogenic recessive diseases in children in a better way.

Monogenic diseases result from mutations in a single gene occurring in all cells of the body. All human beings have two sets or copies of each gene called “alleles”: one copy on each side of the chromosome pair. At the moment of conception a future kid gets one copy of genes from mother and another half from father. That’s why our chromosome count is called diploid.

Recessive diseases are monogenic disorders that occur due to damages in both copies or alleles on homologous chromosomes.

Homologous chromosomes

Fig.1 Two homologous chromosomes: one with defective variant of gene (allele, orange), the other is a normal one (purple)

Although autosomal-recessive diseases are relatively rare, they affect millions of people worldwide as we look closer to genetics. The majority of the population doesn’t even know whether they may carry such mutations in heterozygous state, because one defective allele doesn’t affect their life anyhow. However, when two heterozygotes meet each other the probability of giving birth to a kid with one of these diseases is 25%. As a result, every 100th child worldwide is born with at least one severe genetic pathology.

Recessive diseases

Fig.2 Autosomal-recessive inheritance. If both mother and father carry the same mutation, the probability of giving birth to a healthy, sick and healthy carrier kids are 25%, 25% and 50% respectively.

Our team created a preconceptional screening system as a supplementation to prenatal screening performed in Russia. We analyze 4 of the most frequent monogenic recessive diseases: cystic fibrosis, phenylketonuria and sensorineural hearing loss. The aim of this screening is determination of defective alleles in a pregnancy planning couple.

Preconceptional screening has several advantages over prenatal:

  1. It helps in pregnancy planning, therapeutic abortions reduction thereby contributes a lot to public health
  2. It is noninvasive, so it can't harm neither mother nor fetus
  3. It saves money for heаlthcare system since it helps to give birth to a healthy child and prevent the spread of monogenic diseases in the population

How our iGEM 2020 project works

Genomus predicts the probability of giving birth to a child with an autosomal-recessive disease by comparing genotypes of future parents.

We developed a system which allows people to get their biomaterial tested, receive understandable results and perform comparison with their partner. It’s really easy and intuitive.

To make our project work we had to:

  1. Organize blood or saliva samples donation in Pirogov Medical University
  2. Extract DNA from each sample and develop methods to keep them in order
  3. Design primers & probes for SNP detection and perform qPCR genotyping to analyze the mutations
  4. Develop a secure database with potential parents' genotypes, website and mobile application with algorithms of genotypes comparison using QR-codes for authorized comparison access only
  5. Develop user-friendly notification & pregnancy planning guidance systems


So, to work on Genomus we needed to have access to the lab to keep on working with DNA samples. Unfortunately, because of the COVID-19 pandemics we had to suspend working at our lab.

Fortunately, before the global lockdown we’ve successfully collected approximately 1500 blood and saliva samples of our users, extracted DNA and performed PCR-genotyping.

We couldn’t get into the lab because of the restrictions so we decided to spend this time as productive as possible. For example, we managed to record several interviews for our Human Practices part.

In these interviews we talked to people who are affected by autosomal-recessive diseases. As a result, we’ve come up with the idea to expand analyzed genes because there are lots of other monogenic-recessive mutations. These mutations also need to be diagnosed before the conception.

What are the components of the Genomus?

Genomus is a three-component system. It consists of:

  1. Laboratory
  2. Website with a database
  3. Software for genotypes comparison and notification system.

The first step is fully carried out at Pirogov university’s lab and consists of DNA extraction and qPCR genotyping of biomaterial. We prefer qPCR method because of it’s low price and ease of process automatization.

All the results are loaded to the secure database.

Confidentiality of data is ensured by the fact that there is no virtual connection between users’ personal information (real first name, last name, email), their id-codes and genotypes in a system.

The final step is comparison of a couple's genotypes and informing them about the necessity of visiting a clinical geneticist for a consultation. The notification system has a user-friendly interface which allows people with poor biological and medical background to get relevant information about the risks of giving birth to an unhealthy child.

Technical realization of Genomus

This is how algorithms of the Genomus works:

  1. As soon as we get results after genotyping, we upload them to the database. These results are connected to our users emails and unique identifiers (GENids) which are generated automatically.
  2. After uploading the results, we inform users via email that they can register.
  3. For the registration users enter their emails and GENids, which are handed out privately. This mechanism allows us to provide safety of the personal data. It also ensures that no one except the user will have access to the account.
  4. After the registration on the Genomus website users can change their passwords and other settings. It works almost the same as other websites so the interface is pretty intuitive.
  5. To check out the genotypes compatibility, users need to allow the program to perform comparison via QR-code scanning or GENids. It also acts as additional precaution which allows people to stop comparing at any moment. So, the comparison function works only when two users have this function turned on.
Project scheme

Fig.3 A scheme of how Genomus works. There are 3 main parts: user, lab and server. Users give out their biomaterial, we analyse it at the lab and upload the results to a server where users can find them in their personal accounts.

What mutations do we analyze?

In terms of the iGEM 2020 we focus on analyzing 30 most frequent monogenic recessive mutations in 4 genes. They are the following:

CFTR (cystic fibrosis) PAH (phenylketonuria) GALT (galactosemia) GJB2 (sensorineural hearing loss)
  1. 3944delGT
  2. F508del
  3. K285N
  4. N1303K
  5. 1677delTA
  6. 3849+10kbC>T
  7. E92K
  8. W1282X
  9. G542X
  10. 2143delT
  11. R334W
  12. 394delTT
  13. 2184insA
  14. 3821delT
  15. S466X
  16. dele2,3 (21kb)
  1. R261Q
  2. IVS10nt546
  3. E280K
  4. R408W
  5. P281L
  6. IVS12+1G>A
  7. Y414C
  8. IVS4+5G>T
  9. R158Q
  10. R252W
  11. D222X
  1. N314D
  2. Q188R
  1. 35delG

A brief description of each gene our system Genomus analyzes

CFTR: 7q31.2 = position 31.2 on the long arm of the 7th chromosome

The CFTR gene provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The channel transports negatively charged particles called chloride ions into and out of cells. The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. Mucus is a slippery substance that lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs and tissues.

More than 1,000 mutations in the CFTR gene have been identified in people with cystic fibrosis. Most of these mutations change single protein building blocks (amino acids) in the CFTR protein or delete a small amount of DNA from the CFTR gene.

PAH: 12q23.2, which is the long (q) arm of chromosome 12 at position 23.2

The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase. This enzyme is responsible for the first step in processing phenylalanine, which is an amino acid obtained through the diet.

Phenylalanine hydroxylase is responsible for the conversion of phenylalanine to another amino acid, tyrosine. Tyrosine is used to make several types of hormones, certain neurotransmitters, and a pigment called melanin.

More than 500 mutations in the PAH gene have been identified in people with phenylketonuria. Most of these mutations change single amino acids in phenylalanine hydroxylase. PAH mutations reduce the activity of phenylalanine hydroxylase, preventing it from processing phenylalanine effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.

GALT: 9p13.3 = short (p) arm of chromosome 9 at position 13.3

The GALT gene provides instructions for making an enzyme called galactose-1-phosphate uridylyltransferase. This enzyme enables the body to process a simple sugar called galactose, which is present in small amounts in many foods. Galactose is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas.

Galactose-1-phosphate uridylyltransferase is responsible for one step in a chemical process that breaks down galactose into other molecules that can be used by the body. Specifically, this enzyme converts a modified form of galactose (galactose-1-phosphate) to glucose, which is another simple sugar. Glucose is the main energy source for most cells.

More than 300 mutations in the GALT gene have been identified in people with the classic form of galactosemia, a condition that causes life-threatening signs and symptoms beginning shortly after birth. Most of these mutations severely reduce or eliminate the activity of galactose-1-phosphate uridylyltransferase.

GJB2: 13q12.11, which is the long (q) arm of chromosome 13 at position 12.11

The GJB2 gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between adjoining cells.

Connexin 26 is found in cells throughout the body, including the inner ear. Because of its presence in the inner ear, especially the snail-shaped structure called the cochlea, researchers are interested in this protein's role in hearing. Hearing requires the conversion of sound waves to electrical nerve impulses. This conversion involves many processes, including maintenance of the proper level of potassium ions in the inner ear. Some studies indicate that channels made with connexin 26 help to maintain the correct level of potassium ions. Other research suggests that connexin 26 is required for the maturation of certain cells in the cochlea.

Researchers have identified more than 100 GJB2 gene mutations that can cause nonsyndromic hearing loss, which is loss of hearing that is not associated with other signs and symptoms.