LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 4 of total 4

Search options

  1. Article ; Online: Middle Eastern Genetic Variation Improves Clinical Annotation of the Human Genome

    Sathishkumar Ramaswamy / Ruchi Jain / Maha El Naofal / Nour Halabi / Sawsan Yaslam / Alan Taylor / Ahmad Abou Tayoun

    Journal of Personalized Medicine, Vol 12, Iss 423, p

    2022  Volume 423

    Abstract: Genetic variation in populations of Middle Eastern origin remains highly underrepresented in most comprehensive genomic databases. This underrepresentation hampers the functional annotation of the human genome and challenges accurate clinical variant ... ...

    Abstract Genetic variation in populations of Middle Eastern origin remains highly underrepresented in most comprehensive genomic databases. This underrepresentation hampers the functional annotation of the human genome and challenges accurate clinical variant interpretation. To highlight the importance of capturing genetic variation in the Middle East, we aggregated whole exome and genome sequencing data from 2116 individuals in the Middle East and established the Middle East Variation (MEV) database. Of the high-impact coding (missense and loss of function) variants in this database, 53% were absent from the most comprehensive Genome Aggregation Database (gnomAD), thus representing a unique Middle Eastern variation dataset which might directly impact clinical variant interpretation. We highlight 39 variants with minor allele frequency >1% in the MEV database that were previously reported as rare disease variants in ClinVar and the Human Gene Mutation Database (HGMD). Furthermore, the MEV database consisted of 281 putative homozygous loss of function (LoF) variants, or complete knockouts, of which 31.7% (89/281) were absent from gnomAD. This set represents either complete knockouts of 83 unique genes in reportedly healthy individuals, with implications regarding disease penetrance and expressivity, or might affect dispensable exons, thus refining the clinical annotation of those regions. Intriguingly, 24 of those genes have several clinically significant variants reported in ClinVar and/or HGMD. Our study shows that genetic variation in the Middle East improves functional annotation and clinical interpretation of the genome and emphasizes the need for expanding sequencing studies in the Middle East and other underrepresented populations.
    Keywords Middle East Variants ; whole exome sequencing ; whole genome sequencing ; knockouts ; common variants ; Medicine ; R
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Rapid whole genome sequencing of critically ill pediatric patients from genetically underrepresented populations

    Nour Halabi / Sathishkumar Ramaswamy / Maha El Naofal / Alan Taylor / Sawsan Yaslam / Ruchi Jain / Roudha Alfalasi / Shruti Shenbagam / Martin Bitzan / Lemis Yavuz / Hamda Abulhoul / Shiva Shankar / Dalwinder Janjua / Devendrasing Jadhav / Munira Mahmoud Al Maazmi / Walid Abuhammour / Alawi Alsheikh-Ali / Mohamed Al Awadhi / Abdulla Al Khayat /
    Ahmad N. Abou Tayoun

    Genome Medicine, Vol 14, Iss 1, Pp 1-

    2022  Volume 5

    Abstract: Abstract We describe a case series of five infants (age range: 1–90 days; 4 females and 1 male) who presented to Al Jalila Children’s intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or ... ...

    Abstract Abstract We describe a case series of five infants (age range: 1–90 days; 4 females and 1 male) who presented to Al Jalila Children’s intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or Pakistani. Trio rapid whole genome sequencing (rWGS) was performed on all five patients and their parents within the hospital’s genomics facility. Results were returned within ~37 h from blood sample draws and were diagnostic in 3 out of 5 patients. Positive findings were a homozygous pathogenic variant in POMT1 gene causing muscular dystrophydystroglycanopathy, a mosaic tetrasomy of the short arm of chromosome 12 (12p13.33p11.1) causing Pallister-Killian syndrome, and compound heterozygous pathogenic variants in the LIPA gene causing lysosomal acid lipase deficiency and Wolman disease. The rWGS analysis provided fast and precise diagnostic findings in those 3 patients and also aided in devising better management plans for them in the intensive care setting. For example, the 3-month-old infant with pathogenic variants in the LIPA gene is now a candidate for an FDA-approved, potentially lifesaving enzyme replacement therapy (sebelipase alfa). Our case series emphasize the feasibility and utility of rWGS in pediatric intensive care setting, in a diverse population that has long been underserved in genomic services. Significant investments in local healthcare infrastructure are needed, globally, for more equitable access of genomic medicine among vulnerable patients.
    Keywords Medicine ; R ; Genetics ; QH426-470
    Subject code 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Multiple early introductions of SARS-CoV-2 into a global travel hub in the Middle East

    Ahmad Abou Tayoun / Tom Loney / Hamda Khansaheb / Sathishkumar Ramaswamy / Divinlal Harilal / Zulfa Omar Deesi / Rupa Murthy Varghese / Hanan Al Suwaidi / Abdulmajeed Alkhajeh / Laila Mohamed AlDabal / Mohammed Uddin / Rifat Hamoudi / Rabih Halwani / Abiola Senok / Qutayba Hamid / Norbert Nowotny / Alawi Alsheikh-Ali

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 7

    Abstract: Abstract International travel played a significant role in the early global spread of SARS-CoV-2. Understanding transmission patterns from different regions of the world will further inform global dynamics of the pandemic. Using data from Dubai in the ... ...

    Abstract Abstract International travel played a significant role in the early global spread of SARS-CoV-2. Understanding transmission patterns from different regions of the world will further inform global dynamics of the pandemic. Using data from Dubai in the United Arab Emirates (UAE), a major international travel hub in the Middle East, we establish SARS-CoV-2 full genome sequences from the index and early COVID-19 patients in the UAE. The genome sequences are analysed in the context of virus introductions, chain of transmissions, and possible links to earlier strains from other regions of the world. Phylogenetic analysis showed multiple spatiotemporal introductions of SARS-CoV-2 into the UAE from Asia, Europe, and the Middle East during the early phase of the pandemic. We also provide evidence for early community-based transmission and catalogue new mutations in SARS-CoV-2 strains in the UAE. Our findings contribute to the understanding of the global transmission network of SARS-CoV-2.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: The genomic landscape of rare disorders in the Middle East

    Maha El Naofal / Sathishkumar Ramaswamy / Ali Alsarhan / Ahmed Nugud / Fatima Sarfraz / Hiba Janbaz / Alan Taylor / Ruchi Jain / Nour Halabi / Sawsan Yaslam / Roudha Alfalasi / Shruti Shenbagam / Fatma Rabea / Martin Bitzan / Lemis Yavuz / Deena Wafadari / Hamda Abulhoul / Shiva Shankar / Munira Al Maazmi /
    Ruba Rizk / Zeinab Alloub / Haitham Elbashir / Mohamed O. E. Babiker / Nidheesh Chencheri / Ammar AlBanna / Meshal Sultan / Mohamed El Bitar / Safeena Kherani / Nandu Thalange / Sattar Alshryda / Roberto Di Donato / Christos Tzivinikos / Ibrar Majid / Alexandra F. Freeman / Corina Gonzalez / Arif O. Khan / Hisham Hamdan / Walid Abuhammour / Mohamed AlAwadhi / Abdulla AlKhayat / Alawi Alsheikh-Ali / Ahmad N. Abou Tayoun

    Genome Medicine, Vol 15, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: Abstract Background Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. ... ...

    Abstract Abstract Background Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. Methods We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant. Results We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7–35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7–37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. ...
    Keywords Genomics ; Rare diseases ; Whole-exome sequencing ; Middle East ; Diagnostic yield ; Clinical utility ; Medicine ; R ; Genetics ; QH426-470
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top