Research Cell (BUCM-IC)

Autism spectrum disorder trios from consanguineous populations are enriched for rare homozygous variants, identifying 32 new candidate genes

Thu, 01 Jan 2026 00:00:00 GMT

Autism spectrum disorder trios from consanguineous populations are enriched for rare homozygous variants, identifying 32 new candidate genes Ricardo Harripaul, Ansa Rabia, Nasim Vasli, Anna Mikhailov, Ashlyn Rodrigues, Stephen F. Pastore, Tahir Muhammad, Thulasi Thiruvallur Madanagopal, Aisha Nasir Hashmi, Clinton Tran, Cassandra Stan, Katherine Aw, Clement C. Zai, Maleeha Azam, Saqib Mahmood, Abolfazl Heidari, Raheel Qamar, Leon French, Shreejoy Tripathy, Zehra Agha, Muhammad Iqbal, Majid Ghadami, Susan L. Santangelo, Bita Bozorgmehr, Laila Al Ayadhi, Roksana Sasanfar, Shazia Maqbool, Arsalan Hassan, James A. Knowles, Muhammad Ayub & John B. Vincent Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects about 1 in 54 children worldwide, imposing enormous economic and socioemotional burden on families and communities. Genetic studies of ASD have identified de novo copy number variants (CNVs) and point mutations that contribute significantly to the genetic architecture, but the majority of these studies were conducted in populations unsuited for detecting autosomal recessive (AR) inheritance. However, several ASD studies in consanguineous populations point towards AR as an under-appreciated source of ASD variants. Methods: We used whole exome sequencing to look for rare variants for ASD in 115 proband-mother-father trios from populations with high rates of consanguinity, namely Pakistan, Iran, and Saudi Arabia. Consanguinity was assessed through microarray genotyping. Results: We report 77 candidate single nucleotide variants and indels, with 62% homozygous, 22% autosomal dominant/de novo , and 16% X-linked, in 55 trios. 56% of the variants were loss of function (LoF) or putative LoF (pLoF), and 44% nonsynonymous. We found an enrichment of homozygous variants, both in 16 genes previously reported for AR ASD and/or intellectual disability (ID) and 32 previously unreported AR candidate genes (including DAGLA, ENPP6 , FAXDC2 , ILDR2 , KSR2 , PKD1L1 , SCN10A, SHH, and SLC36A1). We also identified seven candidate homozygous exonic loss CNVs. ACCEPTED MANUSCRIPT ARTICLE IN PRESS ARTICLE IN PRESS Biallelic variants for autism…. Conclusions: The significant enrichment for homozygous variants among individuals with high Froh coefficients, compared with low Froh, either in known or candidate AR genes, confirms that genetic architecture for ASD among consanguineous populations is different to non-consanguineous populations. Assessment of consanguinity may assist in the genetic diagnostic process for ASD. Dr. Aisha Nasir Hashmi IPFP Fellow Research Cell BUCM

RELN biallelic variant as a candidate risk factor in a consanguineous Pakistani family with bipolar disorder and clinical heterogeneity

Thu, 01 Jan 2026 00:00:00 GMT

RELN biallelic variant as a candidate risk factor in a consanguineous Pakistani family with bipolar disorder and clinical heterogeneity Aisha Nasir Hashmi a, b,c, Ricardo S. Harripaul b,d, Tahir Muhammad b,d, Benjamin J. Lowther b, Anna Mikhailov b, Zehra Agha a,e, Raheel Qamar a,f, John B. Vincent b,d,g,*, Maleeha Azam Background: Bipolar disorder (BD) is highly heritable, polygenic, multifactorial, and has complex genetic heterogeneity. This study aimed to identify rare variants contributing to the aetiology of BD in a consanguineous family from Pakistan. Methods: Genome-wide SNP microarray and whole exome sequencing (WES) were used for variant identification in a large BD-affected consanguineous Pakistani family. Results: In family BF04, we identified three main regions of homozygosity-by-descent (HBD) over 1 Mb in length, by far the largest being a 43.6 Mb segment on chromosome 7, and, through WES analysis, found one promising novel homozygous variant in RELN (NM_005045; c.2090G>A; p.(Gly697Asp)), within this HBD region segregating in all the BD-affected members. Conclusion: Based on the clinical and genetic data, the present familial study revealed the plausible contribution of a novel variant of RELN in association with BD in the affected family. The present study's findings are valuable in understanding the genetic basis of the multifactorial phenotype BD and pave a better path for future functional studies. Dr. Aisha Nasir Hashmi IPFP Fellow Research Cell BUCM

Influence of open-top chambers induced climate warming on secondary metabolic profile of culturally and medicinally important plants of Himalaya, Karakoram and Hindukush

Wed, 14 May 2025 00:00:00 GMT

Influence of open-top chambers induced climate warming on secondary metabolic profile of culturally and medicinally important plants of Himalaya, Karakoram and Hindukush Saira Karimi, Muhammad Ali Nawaz, Saadia Naseem, Zahid Ali Plants native to colder climates, higher elevations, or semi-arid regions have more phenolic compounds in their organs. Faced with the current climate crisis, the effects of global heating with overgrazing pressure on natural pastures are not fully recognized in the Himalaya-Karakoram and Hindukush (HKH) region. The objective of this research was to investigate how biological active compound accumulation and concentration of high-elevation plants change under the influence of simulated climate warming which was induced by open-top chambers. The bioactive profiling plant species from experimental units were investigated through High-Performance Liquid Chromatography (HPLC), and compared with control. That revealed a significant increase in the major phenolic acid and flavonoid compounds (Rutin, Quercetin, Myricetin, Gallic Acid, and Kaempferol). The accumulation of other minor compounds, such as Vanillic Acid, Syringic Acid, Ferulic Acid, and Catechin, showed species-specific variation in concentration. The species-specific responses indicated the dominant and positive adaptation species such as P. macrophylla, A. rupestris, A. penduncularis, P. hololeuca, P. alpina, and under stress could accumulate more secondary metabolites, explaining their capacity for adaptation. These species’ proliferation under a stressed climate and higher elevation with grazing pressure provides insightful information about their exploitation of phenolic compounds which may alter the environmental sustainability. Research Assistant Saira Karimi Research Cell

Heamatological and biochemical parameters with different serological status in dengue patients.

Wed, 01 Jan 2025 00:00:00 GMT

Heamatological and biochemical parameters with different serological status in dengue patients. Huma Amin, Shameela Majeed, Wafa Omer, Shumaila Najeeb, Nadia Wali, Fatima tuz Zuhra Objective: To compare the hematological and biochemical parameters of dengue patients within different serological markers. Study Design: Cross Sectional study. Setting: Carried out in a Tertiary Care Hospital at Rawalpindi. Period: August 2023 to December 2023. Methods: Of 250 seropositive dengue cases Hematological analysis was done by Mindray 3000 plus. For biochemical analysis Beckman &coulter, AU480 was used. Subjects were distributed into seven serogroups (NS1 positive, NS1+IgG, NS1+IgM positive, IgM positive, IgG positive, IgG+IgM, NS1, IgM+IgG and triple positive). Results were analyzed using SPSS software, ANOVA test was used, and means were compared in different groups. P value of <0.05 was considered as significant. Results: A total of 178 (71%) among study group were male. Mean age was found to be 37±13.8 years. NS1 antigen either in isolation or in combination was positive in 80%of patient at the time of presentation. The most affected parameters among the whole study cohort were low mean platelet count (81.90±49.2) and higher mean value of ALT (92.81±75.07). The mean value of haematological and biochemical parameters were studied in different serological groups. No significant difference of mean haemoglobin and platelet was observed in between different serological groups however Mean TLC differ significantly within these subgroups (p value = <0.05). The Mean values of various biochemical parameters did not exhibit any significant difference within the different serological groups. Conclusion:Dengue is more prevalent in young population and in males. Thrombocytopenia and elevated ALT levels were most common laboratory finding observed in these patients. NS1 was the most frequent marker at the time of presentation. Only Mean TLC (p value = <0.05) was observed to be significantly different in between different serological groups. Senior Prof Dr Wafa Omer Director Research Pathology BUCM