Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies

A.C.P. da Fonseca; C. Mastronardi; A. Johar; M. Arcos-Burgos; G. Paz-Filho

doi:10.1016/j.jdiacomp.2017.04.026

Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies

A.C.P. da Fonseca, C. Mastronardi, A. Johar, M. Arcos-Burgos, G. Paz-Filho

Universidad del Rosario

Producción científica: Contribución a una revista › Artículo de Investigación › revisión exhaustiva

52 Citas (Scopus)

Resumen

Antecedentes: La obesidad infantil es un grave problema de salud pública asociado con el desarrollo de varias enfermedades crónicas, como la diabetes mellitus tipo 2, la dislipidemia y la hipertensión. La elevada prevalencia de la obesidad se debe principalmente a una dieta y un estilo de vida inadecuados, pero también se debe a factores genéticos: Revisar los avances recientes en el ﬁeld de la genética de la obesidad. Resumimos la lista de genes asociados con las raras formas no sindrómicas de obesidad y explicamos su función. Además, discutimos las tecnologías disponibles para el diagnóstico genético de la obesidad: Varios estudios reportaron que las variantes de un solo gen causan formas mendelianas de obesidad, determinadas por las mutaciones de mayor efecto en un solo gen. Las formas raras y no sindrómicas de obesidad son el resultado de la pérdida de la función de los genes que actúan sobre el desarrollo y la función del hipotálamo o de la vía leptina-melanocortino. Estas variantes alteran las enzimas y los receptores que juegan un papel en la homeostasis de la energía, resultando en obesidad de inicio temprano y disfunciones endocrinas. Se han utilizado diferentes enfoques y tecnologías para comprender el trasfondo genético de la obesidad. Actualmente, el genoma completo y la exomesequenización completa son herramientas diagnósticas importantes para identificar nuevos genes y variantes asociadas con la obesidad severa, pero otros enfoques también son útiles a nivel individual o poblacional, como el análisis de enlaces, la secuenciación de candidatos, el análisis de microarrays cromosómicos y los estudios de asociación a nivel de todo el genoma.Conclusiones: La comprensión de las causas genéticas de la obesidad y la utilidad y las limitaciones de los enfoques de diagnóstico genético pueden contribuir al desarrollo de nuevas dianas terapéuticas personalizadas contra la obesidad.

Idioma original	Inglés estadounidense
Páginas (desde-hasta)	1549-1561
Número de páginas	13
Publicación	Journal of Diabetes and its Complications
Volumen	31
N.º	10
DOI	https://doi.org/10.1016/j.jdiacomp.2017.04.026 https://doi.org/10.1016/j.jdiacomp.2017.04.026 https://doi.org/10.1016/j.jdiacomp.2017.04.026
Estado	Publicada - jun. 16 2017

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da Fonseca, A. C. P., Mastronardi, C., Johar, A., Arcos-Burgos, M., & Paz-Filho, G. (2017). Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies. Journal of Diabetes and its Complications, 31(10), 1549-1561. https://doi.org/10.1016/j.jdiacomp.2017.04.026, https://doi.org/10.1016/j.jdiacomp.2017.04.026, https://doi.org/10.1016/j.jdiacomp.2017.04.026

@article{ea81fb19add0499bba9d9f962c69c3db,

title = "Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies",

abstract = "Background Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors. Objectives To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function. Furthermore, we discuss the technologies that are available for the genetic diagnosis of obesity. Results Several studies reported that single gene variants cause Mendelian forms of obesity, determined by mutations of major effect in single genes. Rare, non-syndromic forms of obesity are a result of loss-of-function mutations in genes that act on the development and function of the hypothalamus or the leptin-melanocortin pathway. These variants disrupt enzymes and receptors that play a role in energy homeostasis, resulting in severe early-onset obesity and endocrine dysfunctions. Different approaches and technologies have been used to understand the genetic background of obesity. Currently, whole genome and whole exome sequencing are important diagnostic tools to identify new genes and variants associated with severe obesity, but other approaches are also useful at individual or population levels, such as linkage analysis, candidate gene sequencing, chromosomal microarray analysis, and genome-wide association studies. Conclusions The understanding of the genetic causes of obesity and the usefulness and limitations of the genetic diagnostic approaches can contribute to the development of new personalized therapeutic targets against obesity. {\textcopyright} 2017 The Authors",

author = "{da Fonseca}, A.C.P. and C. Mastronardi and A. Johar and M. Arcos-Burgos and G. Paz-Filho",

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da Fonseca, ACP, Mastronardi, C, Johar, A, Arcos-Burgos, M & Paz-Filho, G 2017, 'Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies', Journal of Diabetes and its Complications, vol. 31, n.º 10, pp. 1549-1561. https://doi.org/10.1016/j.jdiacomp.2017.04.026, https://doi.org/10.1016/j.jdiacomp.2017.04.026, https://doi.org/10.1016/j.jdiacomp.2017.04.026

TY - JOUR

T1 - Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies

AU - da Fonseca, A.C.P.

AU - Mastronardi, C.

AU - Johar, A.

AU - Arcos-Burgos, M.

AU - Paz-Filho, G.

N1 - Export Date: 4 April 2018 CODEN: JDICE

PY - 2017/6/16

Y1 - 2017/6/16

N2 - Background Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors. Objectives To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function. Furthermore, we discuss the technologies that are available for the genetic diagnosis of obesity. Results Several studies reported that single gene variants cause Mendelian forms of obesity, determined by mutations of major effect in single genes. Rare, non-syndromic forms of obesity are a result of loss-of-function mutations in genes that act on the development and function of the hypothalamus or the leptin-melanocortin pathway. These variants disrupt enzymes and receptors that play a role in energy homeostasis, resulting in severe early-onset obesity and endocrine dysfunctions. Different approaches and technologies have been used to understand the genetic background of obesity. Currently, whole genome and whole exome sequencing are important diagnostic tools to identify new genes and variants associated with severe obesity, but other approaches are also useful at individual or population levels, such as linkage analysis, candidate gene sequencing, chromosomal microarray analysis, and genome-wide association studies. Conclusions The understanding of the genetic causes of obesity and the usefulness and limitations of the genetic diagnostic approaches can contribute to the development of new personalized therapeutic targets against obesity. © 2017 The Authors

AB - Background Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors. Objectives To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function. Furthermore, we discuss the technologies that are available for the genetic diagnosis of obesity. Results Several studies reported that single gene variants cause Mendelian forms of obesity, determined by mutations of major effect in single genes. Rare, non-syndromic forms of obesity are a result of loss-of-function mutations in genes that act on the development and function of the hypothalamus or the leptin-melanocortin pathway. These variants disrupt enzymes and receptors that play a role in energy homeostasis, resulting in severe early-onset obesity and endocrine dysfunctions. Different approaches and technologies have been used to understand the genetic background of obesity. Currently, whole genome and whole exome sequencing are important diagnostic tools to identify new genes and variants associated with severe obesity, but other approaches are also useful at individual or population levels, such as linkage analysis, candidate gene sequencing, chromosomal microarray analysis, and genome-wide association studies. Conclusions The understanding of the genetic causes of obesity and the usefulness and limitations of the genetic diagnostic approaches can contribute to the development of new personalized therapeutic targets against obesity. © 2017 The Authors

U2 - 10.1016/j.jdiacomp.2017.04.026

DO - 10.1016/j.jdiacomp.2017.04.026

M3 - Research Article

C2 - 28735903

SN - 1056-8727

VL - 31

SP - 1549

EP - 1561

JO - Journal of Diabetes and its Complications

JF - Journal of Diabetes and its Complications

IS - 10

ER -

Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies

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