Genetics of obesity - AbsoluteAstronomy.com

Like many other medical conditions, obesity

Obesity

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

is the result of an interplay between genetic and environmental factors. Polymorphism

Polymorphism (biology)

Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...

s in various gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s controlling appetite

Appetite

The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

and metabolism

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

predispose to obesity when sufficient calories are present. The percentage of obesity that can be attributed to genetics varies widely, depending on the population examined, from 6% to 85%. As of 2006, more than 41 sites on the human genome have been linked to the development of obesity when a favorable environment is present.

Genes

Although genetic deficiencies are currently considered rare, variations in these genes may predispose to common obesity. Many candidate genes are highly expressed in the central nervous system

Central nervous system

The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

.

Several additional loci have been identified. Also, several quantitative trait loci for BMI

Body mass index

The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...

have been identified.

Confirmed and hypothesized associations include:

Condition	Locus Locus (genetics) In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...	Notes
leptin Leptin Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones... deficiency	7q31.3
leptin receptor Leptin receptor Leptin receptor also known as LEP-R is a protein that in humans is encoded by the LEPR gene. LEP-R functions as a receptor for the fat cell-specific hormone leptin... deficiency	1p31
prohormone convertase-1 deficiency	5q15-q21
proopiomelanocortin Proopiomelanocortin Pro-opiomelanocortin is a precursor polypeptide with 241 amino acid residues. POMC is synthesized from the 285-amino acid long polypeptide precursor, pre-pro-opiomelanocortin , by the removal of a 44-amino acid long signal peptide sequence during translation.The POMC gene is located on chromosome... deficiency	2p23.3
melanocortin-4 receptor polymorphism (MC4R)	18q22
	7q32.3	near D7S1804
	13q14	near D13S257
	6q23-q25	near D6S1009, GATA184A08, D6S2436, and D6S305
	11q24	near D11S1998, D11S4464, and D11S912
	16p13	near ATA41E04
	20pter-p11.2	near D20S482
INSIG2 INSIG2 Insulin induced gene 2, also known as INSIG2, is a protein which in humans is encoded by the INSIG2 gene.- Regulation :Insulin activates the human INSIG2 promoter in a process mediated by phosphorylated SAP1a....	2q14.1
FTO FTO gene Fat mass and obesity-associated protein also known as alpha-ketoglutarate-dependent dioxygenase FTO is an enzyme that in humans is encoded by the FTO gene located on chromosome 16...	16q12.2	Adults who were homozygous for a particular FTO allele Allele An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation... weighed about 3 kilograms more and had a 1.6-fold greater rate of obesity than those who had not inherited this trait. This association disappeared, though, when those with FTO polymorphisms participated in moderately intensive physical activity equivalent to three to four hours of brisk walking.
TMEM18 TMEM18 Transmembrane protein 18 also known as TMEM18 is a protein which in humans is encoded by the TMEM18 gene.- Function :Overexpression of the TMEM18 protein increases the migration capacity of neural stem cells while inactivation of TMEM18 results in almost complete loss of migration activity.The...	2p25.3
GNPDA2 GNPDA2 Glucosamine-6-phosphate deaminase 2 also known as GNPDA2 is an enzyme that in humans is encoded by the GNPDA2 gene....	4p13
NEGR1 NEGR1 Neuronal growth regulator 1 also known as NEGR1 is a protein which in humans is encoded by the NEGR1 gene....	1p31.1
BDNF	11p13
KCTD15 KCTD15 Potassium channel tetramerisation domain containing 15 also known as BTB/POZ domain-containing protein KCTD15 is protein that in humans is encoded by the KCTD15 gene....	19q13.12
SH2B1 SH2B1 SH2B adapter protein 1 is a protein that in humans is encoded by the SH2B1 gene.-Interactions:SH2B1 has been shown to interact with Insulin receptor, Grb2, TrkA and Janus kinase 2.- Clinical significance :...	16p11.2
MTCH2 MTCH2 Mitochondrial carrier homolog 2 also known as MTCH2 is a protein which in humans is encoded by the MTCH2 gene....	11p11.2
PCSK1	5q15-q21
NPC1 NPC1 Niemann-Pick disease, type C1 also known as NPC1 is a protein which in humans is encoded by the NPC1 gene.NPC1 was identified as the gene that when mutated, results in Niemann-Pick disease, type C...	18q11-q12

Some studies have focused upon inheritance patterns without focusing upon specific genes. One study found that 80% of the offspring of two obese parents were obese, in contrast to less than 10% of the offspring of two parents who were of normal weight.

The thrifty gene hypothesis

Thrifty gene hypothesis

The thrifty gene hypothesis was proposed by geneticist James V. Neel in 1962 to resolve a fundamental problem. Diabetes is clearly a very harmful medical condition. Yet it is quite common, and it was already evident to Neel that it likely had a strong genetic basis...

postulates that due to dietary scarcity during human evolution people are prone to obesity. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would be more likely survive famine

Famine

A famine is a widespread scarcity of food, caused by several factors including crop failure, overpopulation, or government policies. This phenomenon is usually accompanied or followed by regional malnutrition, starvation, epidemic, and increased mortality. Every continent in the world has...

. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. This is the presumed reason that Pima

Pima

The Pima are a group of American Indians living in an area consisting of what is now central and southern Arizona. The long name, "Akimel O'odham", means "river people". They are closely related to the Tohono O'odham and the Hia C-ed O'odham...

Indians, who evolved in a desert ecosystem, developed some of the highest rates of obesity when exposed to a Western lifestyle.

Numerous studies of laboratory rodents provide strong evidence that genetics plays an important role in obesity.

Genetic syndromes

Obesity is also a major feature in several syndromes, such as Prader-Willi syndrome

Prader-Willi syndrome

Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...

, Bardet-Biedl syndrome

Bardet-Biedl syndrome

The Bardet–Biedl syndrome is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.-Summary of the...

, Cohen syndrome

Cohen syndrome

Cohen syndrome is believed to be a gene mutation at locus 8q22 gene COH1. Cohen syndrome has several characteristics such as obesity, mental retardation and craniofacial dysmorphism...

, Ayazi syndrome

Ayazi syndrome

Ayazi syndrome is a syndrome characterized by choroideremia, congenital deafness and obesity.-Symptoms:*Deafness at birth*Obesity*Choroideremia*Impaired vision*Progressive degeneration of the choroid...

, and MOMO syndrome

MOMO syndrome

MOMO syndrome is an extremely rare genetic disorder which belongs to the overgrowth syndromes and has been diagnosed in only six cases around the world, and occurs in 1 in 100 million births. The name is an acronym of the four primary aspects of the disorder: Macrosomia , Obesity, Macrocephaly and...

. (The term "non-syndromic obesity" is sometimes used to exclude these conditions.) In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviation

Standard deviation

Standard deviation is a widely used measure of variability or diversity used in statistics and probability theory. It shows how much variation or "dispersion" there is from the average...

s above normal), 7% harbor a single locus mutation.

Genes

Genetic syndromes

See also