Genetic disorders are medical conditions caused by alternations (mutations) of the genome which leads to the loss, disruption or gain of gene functions[1]. They can arise from inherited mutations, de novo mutations, and somatic mutations. The genetic disorders are categorized into three major types: single-gene or Mendelian disorders, chromosomal disorders, and multifactorial disorders[2]. The therapeutic strategy is based on diagnosis using next-generations sequencing and then target the genetic material in three ways: replacing defective genomes, adding compensatory genetic material, and directly correcting mutations with gene editing[3].
Single-gene disorders, or Mendelian disorder, monogenic disease, monogenic disorder, are caused by mutations in a single gene[4], [5]. The examples of this group include sickle cell disease, cystic fibrosis, polycystic kidney disease, and Tay–Sachs disease[4]. Sickle cell disease, or sickle cell anemia, is the result of a single base-pair point mutation (GAG to GTG) in codon 6 of the human β-globin[6], [7], [8]. The substitution from glutamic acid to valine changes hemoglobin solubility and interactions, leading to polymerization and sickling of red blood cells[9]. Cystic fibrosis, which lead to impaired mucus hydration and clearance and affects more than 100,000 individuals globally, is caused by the mutations in CFTR[10], a protein functioning as chloride channel in the apical membrane of epithelial cells[11]. The common form of polycystic kidney disease is autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in either the PKD1 gene on chromosome 16 or PKD2 gene on chromosome 4[12], [13]. Tay–Sachs disease is an autosomal recessive neurodegenerative disorder, caused by a deficiency of β-hexosaminidase A, leading to impaired degradation of GM2 ganglioside, its accumulation in neuronal lysosomes, and progressive neuronal damage[14], [15].
Peripheral Blood Mononuclear Cells (PBMCs) can promote the research of cell and gene therapy of sickle cell disease.
Airway epithelial cells or bronchial epithelial cells are used in the research on cystic fibrosis
Using renal epithelial cells to investigate polycystic kidney disease, especially the cells from kidney tubules, where cysts form.
Human neurons are provided for the research on Tay–Sachs disease.
SH-SY5Y neuroblastoma cell line is also used as the neuronal model for lysosomal studies.
Cell Models for Thalassemia – K562 ARC0380
K562 cells are useful for studying erythroid differentiation and fetal hemoglobin regulation, but they do not fully model adult β-globin production or patient-specific β-thalassemia pathology.
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[10] M. Shteinberg, I. J. Haq, D. Polineni, and J. C. Davies, “Cystic fibrosis,” The Lancet, vol. 397, no. 10290, pp. 2195–2211, Jun. 2021, doi: 10.1016/S0140-6736(20)32542-3.
[11] D. N. Sheppard and M. J. Welsh, “Structure and Function of the CFTR Chloride Channel,” Physiol. Rev., vol. 79, no. 1, pp. S23–S45, Jan. 1999, doi: 10.1152/physrev.1999.79.1.S23.
[12] P. C. Harris and V. E. Torres, “Polycystic Kidney Disease,” Annual Review of Medicine, vol. 60, no. Volume 60, 2009. Annual Reviews, pp. 321–337, 2009. doi: https://doi.org/10.1146/annurev.med.60.101707.125712.
[13] P. Igarashi and S. Somlo, “Genetics and Pathogenesis of Polycystic Kidney Disease,” J. Am. Soc. Nephrol., vol. 13, no. 9, pp. 2384–2398, Sep. 2002, doi: 10.1097/01.ASN.0000028643.17901.42.
[14] F. Lui, P. K. Ramani, and B. Parayil Sankaran, “Tay-Sachs Disease,” in StatPearls, Treasure Island (FL): StatPearls Publishing, 2025. Accessed: Sep. 10, 2025. [Online]. Available: http://www.ncbi.nlm.nih.gov/books/NBK564432/
[15] J. A. Fernandes Filho and B. E. Shapiro, “Tay-Sachs Disease,” Arch. Neurol., vol. 61, no. 9, p. 1466, Sep. 2004, doi: 10.1001/archneur.61.9.1466.