The people and organizations that use the Mastermind Genomic Search Engine are doing amazing things every day. As Director of Customer Success, I’ve been privileged to hear many inspiring stories from our users. This blog is the first in our new Client Spotlight series, an interview with Fathima Mohammed Ahamed discussing her work in fertility clinical and research settings.
LIZ: Hello, and thank you for joining our first Genomenon Client Spotlight interview! We are delighted to kick off this series, which will highlight the important work of our clients in the area of clinical genomics. I’m Liz Varga, the Director of Customer Success at Genomenon. One of my key roles is interacting with customers who utilize the Mastermind Genomic Search Engine and understanding their experience. I have the pleasure of speaking with Fathima Mohammed Ahamed, and I am very excited to introduce her so that she can share her incredible story with you.
By way of a brief introduction, Ms. Mohammed Ahamed is an experienced technologist, researcher and bioinformatician. She is currently employed at a fertility center in the United Arab Emirates. She received her Bachelor of Science degree in biotechnology, chemistry and zoology from Christ University in India, and her Master of Science in medical biotechnology from Manipal University. She’s also a lifetime member of the All India Medical Laboratory Technologists’ Association.
Today, she will be sharing her perspectives on the unique aspects of genetic disease in the population of the Middle East, the approach to genetic counseling, and her work in the field of reproductive genetics. So, welcome Fathima, and thank you for joining us!
FATHIMA: Thank you so much for having me!
LIZ: I had the pleasure of speaking with you back in December of 2020 after we connected on LinkedIn, and you shared with me your experience of utilizing the Mastermind Genomic Search Engine and other databases during your time working in clinical reporting. Can you tell me a little bit about your work in the clinical setting?
FATHIMA: Yes! I have used Mastermind in a diagnostic lab focused on fertility. We have protocols where we need to understand if specific genetic changes will lead to disease or not. So here, it’s all about evidence. We have a lot of variants and we have to study how they’re associated with the phenotype. To understand the genotype-phenotype relation, then comes our database, with a lot of studies to look for evidence.
When I say evidence, I’m referring to population studies or functional studies, research on how a mutation is going to cause a particular condition. We’re looking for something very precise when it comes to clinical studies. At the end of the day, it’s about the diagnosis of a particular condition. We should be able to identify, “A is causing a condition called B.” We have to come up with something very solid. Obviously, Mastermind has all this available, which makes life very easy.
Additionally, now that we’re doing much more clinical research and discovery, we need even more evidence. When we’re studying genes and how they work, we really need to understand a lot of background and pathology. To get the literature, obviously, we need help. Just Googling it doesn’t work.
Mastermind has helped me a lot. Genomenon is great at helping people, not only in the clinical setting but also the research. It helps to find all the relevant literature, helps us to understand the background, it’s very important.
LIZ: Thank you so much! When we spoke, you talked about the importance of pathogenicity calling, and why that was so important in the work that you did, both in the clinical setting and the research setting. Can you comment on that a little bit more?
FATHIMA: Sure! As I mentioned before, I’m working in a fertility clinic. Imagine a case in which a patient may come to the clinic saying that there is a condition in their family, that there is a known genetic case, something already occurring in the family. That patient cannot afford to have a child with the same condition. At the end of the day, it’s about having a healthy baby; that’s why they’re in the clinic.
It becomes a cycle, the patient is receiving treatment, it’s a whole process, but again, it’s about having a healthy baby. We select an embryo which is not affected with any mutation, a healthy embryo, and the patient can have a healthy child. Because I’m working in a fertility clinic, I’m just giving you that specific perspective. So, imagine another hypothetical situation in which we’re unable to understand what is wrong, or which variant is causing a particular condition, just because we don’t have enough evidence. This can be really bad. That can lead to a situation where we can only tell the patient that we’re not sure if the child will actually have this condition, just because of the lack of evidence — or because, for the evidence that’s already there, we can’t access it. So, we call this making a “wrong call,” without any evidence, and it’s a problem.
LIZ: I can’t imagine making such an important, life-changing decision based on something very vague, or an unclear classification of whether or not it’s disease-causing or a variant of uncertain significance. One of the reasons I love working with Mastermind is that you can find the information so quickly, and you can be very confident that you found all of the information, that you’re not missing something. Have you had any experiences like that, where new information was revealed that really did help you turn a classification?
FATHIMA: Actually, even if you look at genome-wide association catalogues, the representation of certain populations, especially the Middle Eastern population, is very low, which is a problem. We need more of the data, whatever is available. So, if we’re getting, for example, ten publications from some database, we might get a hundred using Mastermind. Definitely, this is more helpful for us, especially when working with a population that’s already underrepresented. Getting more evidence also increases our scientific confidence. We can say, scientifically, that a diagnosis is accurate, it’s not just a random guess. With clinical research studies, we can take our time, but in a diagnostic setting, there’s no chance.
With more evidence, the classification may change. A variant that was previously labeled “variant of uncertain significance” will change to “likely pathogenic,” which is a big jump between classifications. Some of them will even flip over to “pathogenic.” So it’s very important to make the right classification, and for that we depend upon Mastermind and other databases.
LIZ: One thing that you brought up that was very interesting when we talked was the unique aspects in the population. So as you just touched upon, we know that different variants have different frequencies in different ethnic groups, and so sometimes, you not only need to find general information about a variant, but you really need population-specific information. Can you talk a little bit more about the population in the Middle East, and some unique considerations there?
FATHIMA: Yes, the first issue I already discussed, underrepresentation of a certain population. If you just take the database that’s readily available, the representation is really skewed. So imagine you have about 88% of the data for a certain population, and then 7.5% of another, then less than 4% of another. We only have 0.01% for the Middle Eastern population. The database itself already defines populations to this extent. There is a paper published in 2020 from UE Life Sciences that describes this issue in more detail.
Another problem with data retrieval for population-based studies is consanguineous marriages. Consanguinity increases the risk that a child will inherit a genetic disorder if a person’s family history has many consanguineous marriages. We need to identify which mutations in these cases are causing a disorder and which are not, but without external evidence about these mutations, we can’t formally say. We can note that a certain condition is prevalent, but we don’t have any information to say with certainty that a certain mutation is causing a problem. Which is, you know, a very sad scenario, I would say. Not having the proper evidence to say what’s wrong.
So we end up with a lot of founder variants which we see in one particular population. We need to document those, we need more studies, and then we need to link them to other information in the database. The example I brought up earlier, if a researcher working in their own lab with their own data can link their results to Mastermind, you can increase the amount of available data 100-fold. We need to provide that to a database which everyone can explore and understand. Some person at some point using Mastermind can actually find and use that data. It should be linked properly, I think. We already have consanguinity and low representation of a population, so we need something very strong, like Mastermind, to help us with that scenario.
LIZ: Yes, and I do love that one advantage of Mastermind is that it’s agnostic. It’s not dependent on a certain population, it’s just aggregating information that is published. So even for those smaller case studies, we can find that information.
Just for those that might be listening that are a little less familiar with consanguinity — I know some members of my team less familiar with genetics might not be aware of the term, so do you mind just defining what that means exactly?
FATHIMA: Yes, it’s just marriage within a family between two people with a blood relation. When someone marries their first or second cousin, if there is a genetic problem or variant, it will accumulate within the same family. There’s a higher chance for new members of that family to develop more genetic conditions. For example, cases like deafness. There are so many variants for the same genes that accumulate in the family, and we see so many people that are deaf in the same family.
LIZ: Oh, wow.
FATHIMA: Yes, it’s a big deal. Everyone has to go through all the trauma just because of this condition. So it accumulates in the family. It might just be three genes which are responsible for the same phenotype. The variants accumulate in the same family because these marriages happen. There is no variation. There is no diversity. It just accumulates and leads to the disease in a family, which is really sad. So consanguinity is basically getting married with a blood relation, which keeps the same mutations in one family and causes a health condition.
LIZ: Yes, and like you said, it’s even more important for certain inheritance patterns, like recessive conditions that require a certain gene from both the mother’s and the father’s side to cause it. That’s more likely to present itself in those families.
Just based on the frequency of certain disorders in your population, are there conditions that you’re seeing more often than others?
FATHIMA: Yes. We see a lot of G6PD deficiency, anemia or hemolytic anemia, sickle cell diseases, and CFTR variants causing cystic fibrosis and muscular atrophy. These four are the most frequent. And consanguinity is a main factor for this, also, I’d say, because these are all inherited diseases.
LIZ: Right, that makes sense. So tell us a little bit more about your current research focus, and what your role is there.
FATHIMA: Now, it’s mostly infertility genetics, for example, studying the genes that cause embryonic arrest or miscarriages. I’m doing my research work on these conditions, even ovarian failure. It’s a huge interrelated pathway, it’s a very interesting study.
LIZ: Oh, that’s fascinating. Another thing we had talked about was the financial aspect of genetic testing, even for things like infertility treatment. Sometimes in the United States, we can have certain barriers in terms of the funding for genetic testing. It isn’t always covered through private or government insurance. Also, things like infertility treatment might be deemed elective and not medically necessary, so you may not have funding for any of the process. So how does that differ in a country like yours? Is there any governmental funding that supports genetic testing?
FATHIMA: Yes, in the UAE, the financial aspect is really good, I would say – amazing really. Almost everything is insurance covered. The problem is, we need to justify all of our studies. For example, for the whole exome, or the whole genome. Even experts aren’t always aware of when we should go for the analysis part of it. So it’s very important to make them understand the importance of the tests. Not only the funding agency, but also the patients involved in the studies. Patients generally ask simple questions — “Why is this problem happening in the family? What can we do about it? Can you guys assure us that you’ll find the problem? Why don’t we know this yet?” And even if we ask for a family member that has the hereditary problem we’re trying to study, they can be reluctant to participate. So it’s about the information around how important the diagnosis is, rather than the funding. The funding part is well-covered.
LIZ: That’s nice. How about genetic counseling? is that available in your country, is that something that’s done?
FATHIMA: One thing with genetic counseling is the language barrier, a big issue. It’s very difficult with the technical terms and making sure people understand. Even with basic things, you need to be very clear about telling patients why a procedure is being done or what will happen.
For example, a patient with a healthy daughter needs to understand why we need a blood sample from that child, despite the fact that she isn’t having any problems. We have to explain that we’re looking at a specific mutation in the family, otherwise, the patient might misunderstand that to mean we’re trying to find a different disease-causing mutation in the daughter. So we need to clarify that we are looking at a healthy blood sample for comparison, to find out how a given mutation works. We won’t be giving a healthy child treatment for a genetic condition they don’t have. It’s important to make patients understand why this whole process is so important. A genetic counselor plays a very big role in this aspect — on both sides. The counselors even have to justify certain tests to the physicians, as well as explain to the patients why they should be participating in the research.
LIZ: It’s so important. As a former genetic counselor, that was always very fascinating to me, to deal with individuals from different cultural backgrounds and their baseline understanding of genetics. Or just in general, the misconceptions that people have about genetics and inheritance.
I know that when we spoke, you had mentioned to me that you have a lot of different global experiences too, from people that you’ve worked with in different settings. Do you mind telling us just a little bit about your global perspective?
FATHIMA: Sure! Actually, I am from India, so my education and all my initial work was in India. The Indian system has a really strong knowledge base, so there are a lot of evidence-based studies. We have lots of information on different types of indications, different types of cases. My professors and guides who I’ve worked with have amazing knowledge bases, so learning from them is a great experience, even just talking to them. It’s similar to talking to people like you guys, actually, and genetic counselors, people who deal with a lot of different things, which is amazing. Talking to them and understanding how the science works is the most important thing.
In the Middle East, it’s completely different. They’re growing at a very fast pace in terms of research. Even though it’s sort of in its infancy stage, it’s growing. It’s really good to see different people, but the best part here is that it’s a small country, so there are clinical collaborators, academic funding is there. They’re all coordinated very well and groups collaborate often. Everyone is well-connected, especially when it comes to the research or the clinical aspect.
LIZ: You mentioned some of your lab directors have come from different areas, like Spain or Australia or the UK. You get a lot of international influence, no matter where you are, because a lot of times they’ll still be collaborating with colleagues from their home country.
FATHIMA: Yes. They bring their knowledge from different places, and obviously, everything is completely different geographically and culturally. It’s good to brainstorm with people of different backgrounds to understand what’s going on.
LIZ: That’s wonderful. Well, thank you so much! I can’t thank you enough for sharing your time and your perspective. I think it’s just fascinating, and it’s been a privilege to work with you. We’re lucky to have you as a Mastermind client. Is there anything else that you would like to share with us today before we wrap up?
FATHIMA: I would really like to thank the team at Genomenon for helping researchers like me. The clinical aspect is there already, and experts are already giving their feedback on how Mastermind helps them. For me, the more evidence we have, the more scientifically correct we are. It’s really very important to have this kind of initiative. Providing us with this kind of service is amazing. It’s a great job that you experts at Genomenon are doing, so thank you so much for that. Obviously, artificial intelligence and genomic medicine are becoming more related fields at a very fast pace. We need accuracy, we need faster results, we need more understanding and knowledge, and scientifically we should be equipped with everything. So, thank you so much for that.
LIZ: It is such a pleasure. I really look forward to hearing other clinical voices from the genomics community as we go along. Thank you for being my first participant in this!
FATHIMA: Thank you so much! It’s amazing talking to you, understanding your perspective. It’s very important. And thank you for letting me know about all of this — there are so many things that I’m still learning, and it’s experts like you that help me to understand a lot of things in this field.
LIZ: Of course. That’s what I love about the scientific community, we just love to share and exchange information, and we can always learn so much more.
I just want to encourage others, if they want to share their experience just like we did today, they can reach out to us. Otherwise, I’ll just thank you, and we’ll wrap up for today. Have a great rest of your day!
FATHIMA: Thank you!