Amyotrophic lateral sclerosis (ALS) is a progressive and lethal neurodegenerative disorder that is caused by the selective degeneration of upper and lower motor neurons (MNs) in the central nervous system. The causes of ALS are poorly understood and likely to be heterogenous; a compelling approach to understand ALS has been to investigate the 10% of cases with a positive familial history. More than 40 genes have been associated with familial cases. The most common ALS causing gene, C9orf72, has a unique hexanucleotide repeat expansion (HRE) located in the first intron. The hallmark of the C9orf72 pathology includes RNA foci accumulation and translation, and aggregates of repeat-associated dipeptides (DPR) in the nucleus and cell body. In recent years, using 3C-based chromosome conformation technologies, chromatin folding of various cell types, such as fibroblasts, embryonic stem cells (ESC) and neurons, have revealed crucial information to understand 3D folding mechanisms and architectural structures in the nucleus. I performed Hi-C 2.0 and RNA-seq to investigate the three-dimensional genome architectures and transcriptome profiles in three different cell types generated from healthy and ALS individuals with C9orf72 mutation through reprogramming fibroblasts into induced pluripotent stem cells (IPSCs), IPSC differentiation into MNs, and maturation of MNs. Firstly, I analyzed healthy cell types to understand how reprogramming, neural differentiation, and long-term maturation alter genome folding. Secondly, I investigated whether chromatin folding is affected in fibroblasts, IPSCs and MNs of ALS patients with C9orf72 HRE mutation by using the same strategy. This work demonstrated that MNs require long term maturation to establish proper transcriptome and genome folding. Moreover, C9orf72 HRE mutation does not cause any alteration in fibroblast and IPSC lines, however, partial alterations in large scale genome folding were observed in motor neurons.