Advances in biotechnology: genomics and genome editing

Genomics, the study of genes, their functions and related techniques has become a crucial science for developing understanding of life processes and how they evolve. Since the advent of the human genome project, huge strides have been made in developing understanding of DNA and RNA sequence information and how it can be put to good use in the biotechnology sector. Newly derived sequencing and bioinformatics tools have added to the torrent of new insights gained, so that 'sequence once and query often' type DNA apps are now becoming reality. Genome editing, using tools such as CRISPR/Cas9 nuclease or Cpf1 nuclease, provide rapid methods for inserting, deleting or modifying DNA sequences in highly precise ways, in virtually any animal, plant or microbial system. Recent international discussions have considered human germline gene editing, amongst other aspects of this technology. Whether or not gene edited plants will be considered as genetically modified remains an important question. This will determine the regulatory processes adopted by different groups of nations and applicability to feeding the world's ever growing population. Questions surrounding the intellectual property rights associated with gene editing must also be resolved. Mitochondrial replacement therapy leading to '3-Parent Babies' has been successfully carried out in Mexico, by an international team, to correct mother to child mitochondrial disease transmission. The UK has become the first country to legally allow 'cautious use' of mitochondrial donation in treatment. Genomics and genome editing will continue to advance what can be achieved technically, whilst society determines whether or not what can be done should be applied

Genetic testing for Hennekam syndrome

Abstract Hennekam Syndrome (HS) is a combination of congenital lymphatic malformation, lymphangiectasia and other disorders. It is a very rare disorder with autosomal recessive inheritance. We developed the test protocol "Hennekam Syndrome" on the basis of the latest research findings and diagnostic protocols on lymphatic malformation in HS. The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for pulmonary stenosis

Abstract Pulmonary stenosis (PS) is a congenital pulmonary valve malformation. It can be classified as valvular, subvalvular or supravalvular. Isolated forms of PS are rare. PS is associated with the development of massive pulmonary arterial dilatation. Patients with PS have a high consanguinity rate and the disorder is highly familial, which is why knowing the genetic aetiology of this defect is important. Prevalence is estimated at about 4/10,000 live births, and incidence at about 10% of all children with congenital heart defects. PS has prevalently autosomal dominant and rarely autosomal recessive inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for ventricular septal defect

Abstract Ventricular septal defects (VSDs) are the commonest heart malformations and may affect the membranous or the muscular septum. Clinical presentation depends on the amount of interventricular flow, which is determined by the size of the defect and the relative resistances of the pulmonary and systemic vascular beds. The prevalence of VSD is estimated at about 5% among infants. Many small malformations present at birth may later undergo spontaneous closure. VSD may have autosomal dominant or autosomal recessive inheritance and may exist as isolated forms or as part of a syndrome. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for coarctation of aorta

Abstract Coarctation of the aorta (CoA) is an inherited narrowing of the proximal descending thoracic aorta. Histological features include localized medial thickening and infolding with superimposed neointimal tissue. CoA is diagnosed by detection of a murmur or hypertension during routine examination. Typical clinical features are delayed or absent femoral pulses and difference in blood pressure between the arm and legs. These symptoms may appear in the first weeks of life or after the neonatal period. CoA accounts for 4-6% of all congenital heart defects and has a reported prevalence of about 4 per 10,000 live births. It is more common in males than females (59% vs 41%). This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for tetralogy of Fallot

Abstract Tetralogy of Fallot (ToF) combines congenital cardiac defects including ventricular septal defect, pulmonary stenosis, an overriding aorta and right ventricular hypertrophy. Clinical manifestation of this defect depends on the direction and volume of shunting of blood through the ventricular septal defect and the associated right ventricular and pulmonary artery pressures. ToF accounts for 3-5% of congenital heart defects or 0.28 cases every 1000 live births. ToF has autosomal dominant inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for Ebstein anomaly

Abstract Ebstein anomaly (EA) is a rare congenital tricuspid valve malformation, characterized by downward displacement of the septal leaflet and an atrialized right ventricle. About 80% of cases of EA are non-syndromic; in the other 20%, the anomaly is associated with a chromosomal or Mendelian syndrome. The prevalence of EA is estimated at about 1 per 20,000 live births, and accounts for less than 1% of all congenital heart defects. EA has autosomal dominant inheritance. Likely causative genes are: NKX2-5, MYH7 and TPM1. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, potential risk assessment and access to clinical trials

Genetic testing for atrial septal defect

Abstract Atrial septal defect (ASD) is a congenital heart defect characterized by an opening in the atrial septum. About 1/3 of patients with Noonan syndrome caused by mutation in the PTPN11 gene have ASD. The prevalence of ASD is estimated at 100 per 100,000 live births. ASD may have autosomal dominant or recessive inheritance. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for bicuspid aortic valve

Abstract Bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve has two rather than three leaflets. In many patients valve function may be normal but valve decompensation may occur due to other associated congenital abnormalities and secondary valve and aortic complications. Decompensation manifests as stenosis or regurgitation and thoracic aortic aneurysm and dissection. Cystic medial necrosis plays an important role in the pathogenesis of BAV. Prevalence of BAV is estimated at 0.5-2.0%. In children, 70-85% of stenotic aortic valves are bicuspid, compared to at least 50% in adults. BAV has autosomal dominant inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials

Genetic testing for Marfan syndrome

Abstract Marfan syndrome (MFS) is an inherited connective tissue disorder caused by heterozygous mutations in the FBN 1 gene. Clinical manifestations of MFS include aortic dilatation and dissection, as well as cardiac valvular, ocular, skeletal and neurological manifestations. Prevalence varies from 6 to 20 per 100,000 individuals. Revised Ghent Nosology (2010) is used to establish a clinically based suspected diagnosis to be confirmed by molecular testing. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. Molecular testing is useful for diagnosis confirmation, as well as differential diagnosis, appropriate genetic counselling and access to clinical trials