Besides germ cells, each cell of the human body contains 23 pairs (total 46) of chromosomes, which come from father and mother respectively, on a complete set of chromosomes. Each set of chromosomes contains tens of thousands of genes, which are composed of DNA codes. If a change in the process of gene regulation and function affects an individual and causes a disease, and the variation is inherited from the parents, it is called a "genetic disease".
Genetic diseases can be divided into autosomal dominant inheritance, autosomal recessive inheritance and X-linked inheritance according to the inheritance pattern, which is shown in the following figure:
If the father and mother carry the same disease-causing gene, there is a 25% chance of having a baby with the disease.
If the father or mother carries the disease-causing gene, there is a 50% chance of giving birth to a disease baby.
If the mother carries the disease-causing gene on the X chromosome, there is a 25% chance of giving birth to a daughter or son with the disease.
According to the literature:
- 2 out of 10 are known carriers of a recessive genetic disease
- On average, each person carries more than 2 recessively inherited pathogenic genes
The International Rare Disease Database (Orphanet) also shows that about 71.9% of rare diseases are hereditary, and recessive genetic diseases account for 35% of them. Because the carrier is a healthy person with no symptoms at all, even if they carry the disease-causing gene, they ignore the risk of inheriting the disease to the next generation because they have no symptoms. Therefore, the American College of Obstetrics and Gynecology (ACOG) recommends that pre-marital, pre-pregnancy, and prenatal partners or couples can use expanded carrier screen to understand the risk, subsequent progression, and treatment of the disease as soon as possible, so as to avoid giving birth to a diseased baby unprepared.
iGene - Expanded Carrier Screening is to extract DNA from blood samples, and use next-generation sequencing (NGS) technology with bioinformatics analysis software to detect and analyze multiple disease genes at the same time. It is used to detect whether couples or individuals have inherited disease-causing genes. If the test results are high risk, IVF and preimplantation genetic diagnosis (PGD/PGT-M) can be used to give birth to a healthy baby, or to avoid it through the donation of sperm and eggs.
- Premarital, preconception or prenatal partners or couples
- Couples with close blood relations
- Couples who have given birth to a congenitally abnormal baby and are suspected of having a family history of genetic disease
- Individuals want to know whether they have inherited disease-causing genes
- Couples who are preparing to have a healthy baby through artificial reproductive technology
- Egg or Sperm Donor/Recipient
can be divided into 15 categories, which include up to 350 genetic diseases (28 X-linked disease-causing genes)
| Metabolic abnormalities | Phenylketonuria, G6PD Deficiency, Gaucher Disease, Pompe Disease, Wilson Disease, etc |
| Nervous system abnormalities | Spinal Muscular Atrophy, Joubert Syndrome, etc |
| Pulmonary system abnormalities | Cystic Fibrosis, etc |
| Digestive system abnormalities | Progressive Familial Intrahepatic Cholestasis, etc |
| Urinary System abnormalities | Congenital Nephrosis Syndrome, Polycystic Kidney Disease, PKHD1-Related, etc |
| Integumentary system abnormalities | Oculocutaneous Albinism, Lamellar Ichthyosis, Type 1 (Collodion Baby), etc |
| Muscular System abnormalities | Muscular Dystrophy, Nemaline Myopathy, etc |
| Skeletal System abnormalities | Achondrogenesis, Ellis-van Creveld Syndrome, etc |
| Blood abnormalities | Thalassemia, Hemophilia, Congenital Amegakaryocytic Thrombocytopenia, etc |
| Immune system abnormalities | Autoimmune polyendocrinopathy syndrome, Familial Mediterranean Fever, etc |
| Endocrine System abnormalities | Congenital hypothyroidism, Isolated growth hormone deficiency, etc |
| Ocular abnormalities | Achromatopsia, Microphthalmia/Anophthalmia, etc |
| Hearing abnormalities | Non-Syndromic Hearing Loss, Usher Syndrome, etc |
| DNA-repairing abnormalities | Cockayne syndrome, Nijmegen Breakage Syndrome, etc |
| Other diseases | Smith-Lemli-Opitz Syndrome, Hemochromatosis, etc |
※For more info, please visit：iGene gene list
- Expanded carrier screening is done by next generation sequencing (NGS). Large segment deletion, insertion, inversion , duplication or other complicated structural abnormalities can’t be detected.
- iGene only detects genetic diseases listed on the website. If the pathogenic gene variant lands in the non-detectable sequence range, introns or repetitive sequence regions, etc., it cannot be detected.
- iGene can’t screen for genetic mosaicism or autologous mutations that occur after germline union.
A genetic carrier is a person who has no symptoms but carries a recessive disease-causing gene on one of the paired chromosomes. Without any symptoms, the risk of passing the gene to their offspring tends to be overlooked. And the risk is higher if both husband and wife are carriers of the same disease-causing gene than that of the general non-carriers. For genetic carriers, It is suggested to conceive genetic disease-free babies by the help of assisted reproductive technology or donor's eggs/sperms.
Do I need to have an expanded carrier screening?
Statistics show that everyone carries more than 2 recessive disease-causing genes. Recessive gene carriers are usually asymptomatic. If the couple is planning to have children, they can evaluate the risk of illness of the future baby by this test. Only one screening test is needed in a person's lifetime, and it can tell whether each individual has an inherited disease-causing gene.
Should I do the test if there is a suspected family history of genetic disease?
YES. Make sure if one's a genetic carrier earlier in order to understand the risk of the disease earlier, plan the future in advance, and prevent symptom outbreak. Professional counseling is needed after testing positive for any disease-causing genes. And it is suggested that the partner also do the test. If symptoms start to show, it is recommended to consult a genetics specialist for disease diagnosis and follow-up treatment strategies.
Should couples do the test at the same time?
It certainly shortens the waiting timeline. If one of the parties is detected as a carrier, the other party needs to be tested for the risk of the carrier, so testing both parties together can give couples more time to make decisions. If there is sufficient time for planning pregnancy, one party can also be tested first, and after the results confirm whether they carry the disease-causing gene, the subsequent disease risk can be assessed, and then the other party can determine whether further testing is required.
What’s next if I do carry the disease-causing gene?
- If couples can understand their genetic status before trying to conceive, they will have enough time and information to make risk hedging plans. They can decide whether to conceive naturally or not according to the risks, whether IVF and preimplantation genetic diagnosis (PGD/PGT- M) is needed in order to give birth to a healthy baby, or to prevent the disease from being passed on to the next generation by using donor’s sperm/eggs.
- If the couple is already pregnant, it’s suggested to assess the risk of illness of the baby by comprehensive counseling, and conduct prenatal genetic testing for the fetus if necessary.
- If the couple has given birth, the test can make sure whether both parties have the same pathogenic gene, and if necessary, genetic testing of the baby will be carried out.
- If the results show that the inherited pathogenic gene is carried, family relatives may also be at risk of the disease, which can be used as a preventive reference.
It should be considered that this test can only detect pathogenic loci within a pre-selected panel. Although this set includes most of the newborn screening programs in Taiwan, it is still impossible to exclude autologous gene mutations that occur randomly during pregnancy, or pathogenic genes that are not included in the set. If both spouses have negative screening results, it is still recommended to carry out the newborn screening program.