Carrier screening test and ancestry/well-being test, are they the same?

What are carrier screening tests?

Carrier screening tests are analyses designed to determine whether the person being tested is a carrier of a recessive disease. Since it is necessary for a person to receive an altered copy of the same gene with recessive inheritance from both parents to be affected by a recessive disease, the determination of the carrier status of the person being tested makes it possible to know his risk of transmitting a certain disease to his offspring, even if the person being tested does not show any symptoms of the disease, having inherited only an altered copy of the gene.

The aim of the analysis, therefore, is to determine the risk of having offspring affected by a recessive disease by comparing the results of both members of the reproductive couple. If both members of the reproductive couple are identified as carriers of the same disease, it is possible to take informed reproductive decisions that would not have been possible with routine medical testing.

What are ancestry/wellness tests?

Ancestry tests aim to determine the population origins of the person being tested. This information allows the person to discover the ancestral origins of his family beyond the memories provided by his known ancestors. In some cases, it even allows the identification of previously unknown relatives.

The scope of the analysis is to highlight the ethnic mixture of the persons being analyzed, allowing a more global view of their family history, as well as the origin of some of their physical traits.

In some cases, ancestry tests also include genetic analysis related to wellbeing, such as pharmacological compatibility tests or predisposition to certain diseases. Always keeping in mind that these are results in a predisposition environment, so a medical evaluation is required to assess whether the person tested will be at risk of suffering any symptoms of the diseases for which an increased risk in comparison to the general population has been identified.

This information allows the person who undergoes the analysis to evaluate other ways to improve their well-being based on the variations identified in their genes, always considering the need to discuss the results with a specialized physician and the importance of leading a healthy lifestyle regardless of the possible genetic predispositions identified.

What do both tests have in common?

Both tests are based on the massive sequencing analysis of regions of interest in our genome. The analysis of the sequencing results is performed by comparison with a worldwide consensus human reference genome obtained by analyzing the sequences of thousands of people to determine which sequences are common and which sequences are identified in a small percentage of the population. The variations of the analyzed genome with respect to the reference genome are those that will be relevant to the analysis and will be reported in the context of the aim of the analysis.

What is the difference between the two tests?

Although in both cases the focus of the analysis is on the variations in relation to the reference genome used, in the case of carrier screening tests the variations of interest are those that are identified in a small percentage of the population and are localized in genes that have been described in relation to diseases with recessive inheritance. In contrast, in the case of ancestry tests, the variations of interest are those that are observed more frequently in one population than in another. These variations can be located in any region of the genome and, depending on their frequency and quantity, allow the identification of the percentage of ancestry contribution of each ethnic group to the person being analyzed. The variations that determine predisposition to certain diseases or pharmacological compatibility are variations that have been identified in greater frequency in people who have experienced certain symptomatology or response to drugs with respect to people who have not shown symptoms or who have obtained a different response to drugs.

In addition to the technical differences, there are also clear differences in the purpose of the tests and their clinical applications. Carrier screening tests must be prescribed by a physician or genetic counselor with the aim to improve the reproductive health of patients, whereas ancestry/wellness tests do not require a physician’s prescription.

By |2022-09-27T09:03:11+00:0009/09/2022|Uncategorized|0 Comments

May 8, International Thalassemia Day. What you need to know?

What are Thalassemias?

Thalassemia is a term that encompasses different diseases with a common symptomatology, anemia. Anemia is caused by a decrease in the production of functional hemoglobin, the oxygen-carrying molecule in the blood, causing a decrease in red blood cells.

Thalassemias can be classified according to the affected chain or the severity of the disease. In terms of the affected chain, the most common are alpha and beta, caused by pathogenic variants in the HBA1/2 or HBB genes, respectively.

Regarding the severity of alpha thalassemia, 4 types can be defined from less to more severe: silent alpha thalassemia, alpha thalassemia minor, hemoglobin H disease (HbH), and hydrops fetalis with Bart’s Hb. In the case of beta-thalassemia, 3 types can be distinguished: minor, intermediate and major.

Milder forms of the disease are usually asymptomatic, while more severe forms require frequent blood transfusions. If untreated, the most severe forms of the disease appear during the first years of life, showing a lack of appetite, with slow growth and enlargement of organs such as the liver and heart. These symptoms often lead to death during infancy. Intermediate forms generally consist in anemia of varying severity, but rarely require blood transfusions.

Alpha and beta thalassemias are inherited diseases that are transmitted in an autosomal recessive manner. Consequently, it is necessary that both parents of an affected person are carriers of the same disease (either alpha or beta), being affected with silent or minor thalassemia, so that the affected person with an intermediate or severe form of the disease inherits two altered copies of the same gene.

The most common form of the disease is silent or minor thalassemia (disease carriers), while most thalassemia patients with clinical symptoms show intermediate forms of the disease (HbH or beta thalassemia intermedia).

How are they diagnosed?

Approximately 100,000 people worldwide are diagnosed with severe forms of thalassemia each year. Diagnosis of thalassemias is usually made by blood tests. In patients with milder symptomatology, the diagnosis is usually made on routine testing in adulthood during an episode of anemia, while more severe cases are diagnosed during the first months of life because of signs and symptoms resulting from severe anemia.

In mild or asymptomatic cases, carriers of the disease can be diagnosed by genetic testing. However, although less common, as there are more genes and regions involved in thalassemia, it is recommended to complement the genetic analysis with hemoglobin electrophoresis to confirm negative results.

Is there a treatment?

Mild forms of the disease (silent or minor thalassemia) usually do not require treatment as they rarely show symptoms of the disease or occasionally have mild anemia. They generally have a healthy life without being affected by their carrier status.

More severe forms of the disease require regular blood transfusions along with antibiotics. Since regular blood transfusions result in iron overload it is also necessary to complement the treatment with iron chelators. In these cases the disease can also be treated by bone marrow transplantation.

How can the risk of affected offspring be reduced?

As these are recessively inherited diseases, they can be prevented in the offspring by testing for the HBA1, HBA2 and HBB genes in both members of the couple with reproductive desire. If both partners are identified as carriers of pathogenic variants in the same gene (HBA1/2 or HBB) it is possible to reduce the risk of severe forms of the disease in the offspring by preimplantation diagnosis (PGT-M), prenatal diagnosis or gamete donation with genetically screened donors identified as non-carriers of the disease.

If one or both members of the couple are not identified as carriers of pathogenic variants in the analyzed genes, the risk of the child being affected by severe forms of the disease is reduced by lowering the possibility of inheriting all the copies of the same gene with alterations that can lead to disease.

By |2022-09-27T09:02:22+00:0009/09/2022|Uncategorized|0 Comments

Monogenic diseases, what are they and how are they inherited?

Monogenic diseases are caused by alterations in genes, which are structural units that code for proteins and other necessary molecules to make our organism function. Most of our genes are found in the nucleus of our cells organized in the form of chromosomes. People have 23 pairs of chromosomes, 22 autosomal (identical in both genders) and 1 pair of sex chromosomes (which vary according to gender, XX in females and XY in males). Each chromosome from a pair is inherited from a parent. In addition to nuclear DNA, our cells also have DNA within organelles called mitochondria. Mitochondria are inherited exclusively from the mother, so all the genetic material within them also comes from the mother.

Broadly speaking, monogenic diseases can be divided according to the type of inheritance. Thus, there are different types depending on whether the causative gene is located on an autosome chromosome, on a sex chromosome or in the mitochondrial DNA.

Autosomal recessive diseases are those in which in order to show symptoms of the disease it is necessary for the person to inherit both copies of an altered gene. In these cases, both parents must have a normal copy of the gene on one chromosome and an altered copy on the other. They are usually “hidden” diseases, with no family history, since carriers of a healthy copy, such as the parents mentioned above, do not usually show symptoms of the disease as the normal copy maintains the function of the gene. One of the best-known diseases with this type of inheritance is Cystic Fibrosis.

Within the autosomal recessive diseases there is a subtype of inheritance called digenic inheritance: in this case, in order to show the disease, it is not necessary for the person to have both copies of the same gene altered, but it is sufficient to have an altered copy of each of the genes that make up the digenic pair. For example, in the case of the CDH23 and PCDH15 genes, related to Usher syndrome and deafness, a person who is a carrier of only one altered copy of each of these genes may show symptoms of the disease, even if he also has a healthy copy of the CDH23 gene and a healthy copy of the PCDH15 gene.

In the case of autosomal dominant diseases, it is sufficient to inherit a single altered copy of the gene to show symptoms. This copy can come from either parent, who is usually also affected. If one parent is affected by a disease with an autosomal dominant inheritance, 50% of his offspring will inherit the altered copy of the gene and, consequently, will be affected by the same disease. Due to their severity, this type of disease is not usually inherited from the parents; as they are normally caused by de novo alterations, namely they are generated in the gametes or in the embryo in the early stages of its development. One of the best-known diseases with this type of inheritance is achondroplasia (dwarfism).

As for the genes packed in the sex chromosomes, the most common diseases are recessive X-linked inheritance diseases. In this type of diseases, it is necessary for the person to inherit all of his or her altered X chromosome copies. In the case of males, who have only one copy of the X chromosome, they will show symptoms if they inherit one copy of the X chromosome with the altered gene. This altered copy will be inherited from the mother as the father will contribute with the Y chromosome. For this same reason affected males cannot transmit these diseases to their sons. In the case of females, unlike males, since they have two X chromosomes, it is generally necessary for them to inherit an altered copy from both parents in order to show symptoms. However, since there is a phenomenon of inactivation of the X chromosome that does not occur in autosomes, some females may show symptoms with only one altered copy. Depending on the degree of inactivation of the healthy X chromosome, the symptoms tend to be more or less severe, but usually milder than the symptoms presented by males. One of the best-known diseases with this type of inheritance is Haemophilia A and B.

X-linked diseases can also have X-linked dominant inheritance. In these diseases, for the person to show symptoms of the disease, it is sufficient for him to have one copy of the X chromosome with the altered gene. As in the case of autosomal dominant diseases, this type of disease is often caused by a de novo alteration. However, they can also be transmitted between generations. Affected females will transmit the disease to 50% of their offspring. This type of disease is often lethal in men, as they do not have any healthy copies of the affected gene and the symptoms are significantly aggravated. Incontinentia pigmentosa would be a disease with this type of inheritance.

Finally, there are diseases with mitochondrial inheritance, caused by gene alterations found in the DNA of the mitochondria. Since mitochondria are exclusively inherited from the mothers, these diseases are only transmitted from mother to child. It should be noted that within each cell we have many mitochondria and not all of them are carriers of the disease, so depending on the proportion of altered mitochondria that are inherited, the descendants will show symptoms of the disease with more or less severity or may not even show symptoms. One of the best-known diseases with this type of inheritance is Leber’s hereditary optic neuropathy.

Finally, there are also alterations that may imply that the person has a predisposition to develop a disease, although the fact of being a carrier of an altered copy of the gene does not imply that the patient is affected. This would be the case of some genes related to cancer, such as BRCA1, in which between 55% and 72% of women carrying a pathogenic variant in this gene develop breast cancer during their lifetime. In other words, being carriers of a variant in this gene makes it much more likely that they will develop the disease, although not all of them will develop it. Since being a carrier of variants in these genes confers predisposition, but not a certainty of suffering the disease, these diseases can be transmitted from carrier parents without symptoms to affected children. Symptoms usually appear in adulthood, so the influence of environmental factors cannot be ruled out.

There are other types of inheritance of diseases due to genetic causes such as inheritance linked to the Y chromosome or pseudoautosomal inheritance, which are extremely rare.

By |2022-09-27T09:01:44+00:0009/09/2022|Blog, Blog, Blog, Blog|0 Comments

February 28: world day of rare diseases, more common than we think

What are considered rare diseases?

Rare diseases are generally considered to be those diseases that have a low prevalence in the population. Depending on the region, different prevalence have been established to consider a disease as rare, for example, the European Union has considered a prevalence of 5 per 10,000 people to consider a disease as rare. Other countries have more restrictive criteria, such as Japan, where diseases with less than 4 cases per 10,000 habitant are considered rare, or the United States, where a disease is considered rare if less than 200,000 cases are described in the whole country.

According to the World Health Organization (WHO), nearly 7,000 rare diseases have been already described and to this day, more diseases continue to be described in the scientific literature. Therefore, although each of these diseases affects a small group of people, the total number of people affected by a rare disease is around 7% of the population. For example, in Spain it is estimated that there are more than 3 million people affected by a rare disease.

What are the characteristics of rare diseases?

Most rare diseases are severe, chronic, progressive and usually appear in paediatric age, although some diseases are diagnosed in adulthood. In general, there is a higher prevalence in adulthood due to excess infant mortality among those affected by rare diseases.

At least 75% of rare diseases have a genetic origin, the rest of the causes being very diverse, for example, there are autoimmune diseases, some types of cancers or infectious diseases that are very infrequent.

What does it mean to be affected by a rare disease?

The diagnosis of a rare disease can take years and sometimes they are diagnosed incorrectly due to the lack of knowledge of these pathologies. On average, it takes a patient 4 years to obtain a diagnosis. In 31% of cases, the lack of diagnosis causes a worsening of the disease symptoms that could have been avoided with an early diagnosis. This lack of diagnosis also often hinders treatment for rare diseases, causing up to 42.68% of patients to have no treatment or to receive inadequate treatment.

People affected by rare diseases often see their life quality affected, as these kind diseases often cause chronic pain, physical or intellectual disabilities or senses impairment such as blindness or or deafness.

What initiatives exist for the visualization of these diseases?

The European Organization for Rare Diseases (EURORDIS) celebrates the Mundial day for Rare Diseases on February 28th, with the aim of raising awareness of these diseases and the need for research to be put into them.

In Spain, the Spanish federation of rare diseases (FEDER) has as a task “To represent and defend the rights of people with a rare disease and suspected diagnosis, favouring their inclusion and generating strategies that contribute to improve their quality of life.”

Currently, carrier screening tests aim to reduce the risk of having a child affected by the most prevalent genetic rare diseases with a known cause. By determining the healthy carrier status of forthcoming parents and determining the risk of having a child affected by one of the diseases screened for. If a high risk is detected, couples can decide alternatives such as preimplantation diagnosis, prenatal diagnosis or early diagnosis from birth, facilitating the application of appropriate treatment.

By |2022-09-27T09:00:59+00:0009/09/2022|Uncategorized|0 Comments
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