Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sheth Harsh, Nair Aadhira, Bhavsar Riddhi, Kamate Mahesh, Gowda Vykuntaraju K, Bavdekar Ashish, Kadam Sandeep, Nampoothiri Sheela, Panigrahi Inusha, Kaur Anupriya, Shah Siddharth, Mehta Sanjeev, Jagadeesan Sujatha, Suresh Indrani, Kapoor Seema, Bajaj Shruti, Devi Radha Rama, Prajapati Ashka, Godbole Koumudi, Patel Harsh, Luhar Zulfiqar, Shah Raju C, Iyer Anand, Bijarnia Sunita, Puri Ratna, Muranjan Mamta, Shah Ami, Magar Suvarna, Gupta Neerja, Tayade Naresh, Gandhi Ajit, Sowani Ajit, Kale Shrutikaa, Jalan Anil, Solanki Dhaval, Dalal Ashwin, Mane Shrikant, Prabha C Ratna, Sheth Frenny, Joshi Chaitanya G, Joshi Madhvi, Sheth Jayesh
Аннотация
RESULTS: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood.
CONCLUSION: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.