Limitations of short-read sequencing: 

• Generates reads that are often too short to map accurately to specific regions of the reference genome. If the reads can't be mapped, they might be discarded, creating gaps in the sequencing data.
• Repeat expansion disorders are hard to detect accurately, especially if the repeat regions are longer than the read length. 
• Can be challenging to sequence genes that have a pseudogene or genes that are in repetitive regions.  
• Is not as effective at detecting structural variants and large copy number variants as compared to methods such as karyotyping or arrays.
• Methylation changes, which need specific studies, are not detected by short-read sequencing.