Gene composition for screening difficult hereditary bone diseases, chip and kit

Abstract

The invention provides a gene composition for screening difficult hereditary bone diseases, a chip and a kit. The gene composition comprises 322 hereditary bone disease related pathogenic genes. According to the gene composition related to the hereditary bone diseases and the related products (gene chip and kit) thereof, aiming at the requirement that difficult bone diseases are difficult to diagnose and treat in China, genome sequencing and big data analysis are combined on the basis of understanding the hereditary bone diseases in the prior art, a targeted capture sequencing kit for diagnosing various hereditary bone diseases is developed, and the kit has the advantages that probes can be flexibly customized, target genes and regions can be specifically captured, and particularly, capture sequencing can also be carried out in pathogenic regions not contained in WES; regions which cannot be captured by the WES can be supplemented and optimized, a better capturing effect is achieved, the coverage rate is high, and the variation detection precision is high; the cost performance is higher, the clinical detection is faster, and the cost is lower.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a gene composition, a chip and a kit for screening difficult hereditary bone diseases. Background technique [0002] Hereditary bone diseases refer to hereditary diseases that cause abnormal bone development due to changes in genetic factors. The clinical phenotypes include growth retardation, short stature, long bone deformity, and limited joint mobility. The clinical and genetic heterogeneity is large. Although their incidence rate is low, their teratogenic and disability rates are high. Most of them are diagnosed in childhood and will be inherited from generation to generation or from generation to generation, which brings huge mental and economic burdens to patients and their families. Therefore, a clear diagnosis is of great significance for the follow-up treatment and eugenics of patients. [0003] At present, clinicians' diagnosis of hereditary bone diseases is generally base...

AI Technical Summary

Problems solved by technology

[0003] At present, clinicians' diagnosis of hereditary bone diseases is generally based on the patient's clinical history, laboratory test indicators, imaging examinations and genetic testing, but most patients with hereditary bone diseases have not received a clear diagnosis and adequate treatment. There are several specific reasons: 1. Until 2019, a total of 461 kinds of hereditary bone diseases have been discovered. There are many types of bone diseases and they are relatively rare. Without systematic training, the lack of understanding of such diseases leads to the inability to make a definite diagnosis; 2. Some bone disease phenotypes overlap among genetic bone diseases, and most genetic bone diseases will manifest as short stature, but lead to short stature The causes are different, and achondroplasia, spinal epiphyseal dysplasia, and pseudochondroplasia can all have short stature; 3. Hereditary bone diseases have high genetic heterogeneity, and the same disease can have multiple pathogenesis Genes, such as osteogenesis imperfecta, can be caused by multiple gene mutations such as COL1A1, COL1A2, IFITM5, FKBP10, etc. Clinically, it is often only possible to make a general diagnosis based on the patient's medical history, and it is impossible to carry out individualized treatment according to the specific type; the same gene mutation leads to different Types of diseases, such as COL2A1 gene mutations can lead to spinal epiphyseal dysplasia, multiple epiphyseal dysplasia with vision and hearing impairment, Kniest bone dysplasia and other diseases, which add great difficulty to diagnosis

[0004] There are many causative genes for hereditary bone diseases, and doctors are often unable to accurately locate the causative genes. They need to sequence the candidate genes one by one to determine whether the disease is caused or not, which virtually increases the cost and time of sequencing

Moreover, during the sequencing process, the sequencing data will contain an excessively large proportion of N, a high proportion of bases with low sequencing quality, sequence pollution, etc. will lead to a decrease in the quality of reads, affecting subsequent analysis, and high GC content resulting in coverage Poor, low capture rate

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