Cognitive genomics (or neurative genomics) is the sub-field of

genomics Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...

pertaining to cognitive function in which the

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s and non-coding sequences of an organism's

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

related to the health and activity of the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

are studied. By applying

comparative genomics Comparative genomics is a field of biological research in which the genomic features of different organisms are compared. The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural lan ...

, the genomes of multiple species are compared in order to identify genetic and

phenotypical In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

differences between species. Observed phenotypical characteristics related to the neurological function include

behavior Behavior (American English) or behaviour (British English) is the range of actions and mannerisms made by individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as wel ...

personality Personality is the characteristic sets of behaviors, cognitions, and emotional patterns that are formed from biological and environmental factors, and which change over time. While there is no generally agreed-upon definition of personality, mos ...

neuroanatomy Neuroanatomy is the study of the structure and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defin ...

, and

neuropathology Neuropathology is the study of disease of nervous system tissue, usually in the form of either small surgical biopsies or whole-body autopsies. Neuropathologists usually work in a department of anatomic pathology, but work closely with the clinic ...

. The theory behind cognitive genomics is based on elements of

genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...

evolutionary biology Evolutionary biology is the subfield of biology that studies the evolutionary processes (natural selection, common descent, speciation) that produced the diversity of life on Earth. It is also defined as the study of the history of life fo ...

molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

cognitive psychology Cognitive psychology is the scientific study of mental processes such as attention, language use, memory, perception, problem solving, creativity, and reasoning. Cognitive psychology originated in the 1960s in a break from behaviorism, which ...

behavioral psychology Behaviorism is a systematic approach to understanding the behavior of humans and animals. It assumes that behavior is either a reflex evoked by the pairing of certain antecedent stimuli in the environment, or a consequence of that individual ...

, and

neurophysiology Neurophysiology is a branch of physiology and neuroscience that studies nervous system function rather than nervous system architecture. This area aids in the diagnosis and monitoring of neurological diseases. Historically, it has been dominated b ...

Intelligence Intelligence has been defined in many ways: the capacity for abstraction, logic, understanding, self-awareness, learning, emotional knowledge, reasoning, planning, creativity, critical thinking, and problem-solving. More generally, it can b ...

is the most extensively studied behavioral trait. In humans, approximately 70% of all genes are expressed in the brain. Genetic variation accounts for 40% of phenotypical variation. Approaches in cognitive genomics have been used to investigate the genetic causes for many mental and

neurodegenerative A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

disorders including

Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...

autism The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

, and

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

Cognitive genomics testing

Approaches

Evo-geno

The most commonly used approach to genome-investigation is evolutionary genomics biology, or evo-geno, in which the genomes of two species which share a common ancestor are compared. A common example of evo-geno is comparative cognitive genomics testing between humans and chimpanzees which shared an ancestor 6-7 million years ago. Patterns in local

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

and

gene splicing Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...

are examined to determine genomic differentiation. Comparative transcriptomic analyses conducted on primate brains to measure gene expression levels have shown significant differences between human and chimpanzee genomes. The evo-geno approach was also used to verify the theory that humans and non-human primates share similar expression levels in energy metabolism-related genes which have implications for aging and neurodegenerative disease.

Evo-devo

Evolutionary development biology (evo-devo) approach compares cognitive and neuroanatomic development patterns between sets of species. Studies of human

fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...

brains reveal that almost a third of expressed genes are regionally differentiated, far more than non-human species. This finding could potentially explain variations in cognitive development between individuals. Neuroanatomical evo-devo studies have connected higher brain order to

brain lateralization A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

which, though present in other species, is highly ordered in humans.

Evo-pheno and evo-patho

Evolutionary phenotype biology (evo-pheno) approach examines phenotype expression between species. Evolutionary pathology biology (evo-patho) approach investigates disease prevalence between species.

Imaging genomics

Candidate gene selection

In genomics, a gene being imaged and analyzed is referred to as a candidate gene. The ideal candidate genes for comparative genomic testing are genes that harbor well-defined functional polymorphisms with known effects on neuroanatomical and/or cognitive function. However, genes with either identified single-nucleotide polymorphisms or allele variations with potential functional implications on neuroanatomical systems suffice. The weaker the connection between the gene and the phenotype, the more difficult it is to establish causality through testing.

Controlling for non-genetic factors

Non-genetic factors such as age, illness, injury, or substance abuse can have significant effects on gene expression and phenotypic variance. The identification and contribution of genetic variation to specific phenotypes can only be performed when other potential contributing factors can be matched across genotype groups. In the case of neuroimaging during task performance such as in fMRI, groups are matched by performance level. Non-genetic factors have a particularly large potential effect on cognitive development. In the case of autism, non-genetic factors account for 62% of disease risk.

Task selection

In order to study the connection between a

candidate gene The candidate gene approach to conducting genetic association studies focuses on associations between genetic variation within pre-specified genes of interest, and phenotypes or disease states. This is in contrast to genome-wide association studies ...

and a proposed phenotype, a subject is often given a task to perform that elicits the behavioral phenotype while undergoing some form of

neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incre ...

. Many behavioral tasks used for genomic studies are modified versions of classic behavioral and

neuropsychological Neuropsychology is a branch of psychology concerned with how a person's cognition and behavior are related to the brain and the rest of the nervous system. Professionals in this branch of psychology often focus on how injuries or illnesses of ...

tests designed to investigate neural systems critical to particular behaviors.

Species used in comparative cognitive genomics

Humans

In 2003, the

Human Genome Project The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a ...

produced the first complete human genome. Despite the project’s success, very little is known about cognitive gene expression.Interview with Todd Preuss, PhD, Yerkes National Primate Research Center Prior to 2003, any evidence concerning human brain connectivity was based on

post-mortem An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any dis ...

observations. Due to ethical concerns, no invasive

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

genomics studies have been performed on live humans.

Non-human primates

As the closest genetic relatives to humans,

non-human primates Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...

are the most preferable genomics imaging subjects. In most cases, primates are imaged while under

anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...

. Due to the high cost of raising and maintaining primate populations, genomic testing on non-human primates is typically performed at primate research facilities.

Chimpanzees

Chimpanzee The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close relative th ...

s (''

Pan troglodytes The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of Hominidae, great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close r ...

'') are the closest genetic relatives to

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

s, sharing 93.6% genetic similarity. It is believed that humans and chimpanzees shared a common genetic ancestor around 7 million years ago. The movement to sequence the chimpanzee genome began in 1998 and was given high priority by the US National Institutes of Health (NIH). Currently, human and chimpanzees have the only sequenced genomes in the extended family of primates. Some comparisons of autosomal intergenic non-repetitive DNA segments suggest as little as 1.24% genetic difference between humans and chimpanzees along certain sections. Despite the genetic similarity, 80% of proteins between the two species are different which understates the clear phenotypical differences.

Rhesus macaques

Rhesus macaque The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies that are split between two groups, the Chinese-derived and the Indian-derived. Generally b ...

s (''Macaca mulatta'') exhibit a 93% genetic similarity to humans approximately. They are often used as an out-group in human/chimpanzee genomic studies. Humans and rhesus macaques shared a common ancestor an estimated 25 million years ago.

Apes

Orangutans Orangutans are great apes native to the rainforests of Indonesia and Malaysia. They are now found only in parts of Borneo and Sumatra, but during the Pleistocene they ranged throughout Southeast Asia and South China. Classified in the genus ' ...

(''

Pongo pygmaeus The Bornean orangutan (''Pongo pygmaeus'') is a species of orangutan endemic to the island of Borneo. Together with the Sumatran orangutan (''Pongo abelii'') and Tapanuli orangutan (''Pongo tapanuliensis''), it belongs to the only genus of grea ...

'') and

gorillas Gorillas are herbivorous, predominantly ground-dwelling great apes that inhabit the tropical forests of equatorial Africa. The genus ''Gorilla'' is divided into two species: the eastern gorilla and the western gorilla, and either four or fi ...

(''

Gorilla gorilla The western gorilla (''Gorilla gorilla'') is a great ape found in Africa, one of two species of the hominid genus ''Gorilla''. Large and robust with males weighing around , the hair is significantly lighter in color than the eastern gorilla, '' ...

'') have been used in genomics testing but are not common subjects due to cost.

Neurobehavioral and cognitive disorders

Despite what is sometimes reported, most behavioral or pathological phenotypes are not due to a single

gene mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...

but rather a complex genetic basis. However, there are some exceptions to this rule such as

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...

which is caused by a single specific genetic disorder. The occurrence of neurobehavioral disorders is influenced by a number of factors, genetic and non-genetic.

Down syndrome

Down syndrome is a genetic syndrome marked by

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

and distinct cranio-facial features and occurs in approximately 1 in 800 live births. Experts believe the genetic cause for the syndrome is a lack of genes in the 21st chromosome. However, the gene or genes responsible for the cognitive phenotype have yet to be discovered.

Fragile-X syndrome

Fragile-X syndrome is caused by a mutation of the FRAXA gene located in the

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...

. The syndrome is marked by intellectual disability (moderate in males, mild in females), language deficiency, and some

autistic spectrum The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

behaviors.

Alzheimer’s disease

Alzheimer’s disease is a neurodegenerative disorder that causes age-correlated progressive cognitive decline.

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

using mice have investigated the pathophysiology and suggest possible treatments such as

immunization Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen). When this system is exposed to molecules that are foreign to the body, called ''non-sel ...

with

amyloid beta Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...

and peripheral administration of

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

against amyloid beta. Studies have linked Alzheimer’s with gene alterations causing SAMP8

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

abnormalities.

Autism

Autism is a pervasive developmental disorder characterized by abnormal social development, inability to empathize and effectively communicate, and restricted patterns of interest. A possible neuroanatomical cause is the presence of tubers in the temporal lobe. As mentioned previously, non-genetic factors account for 62% of autism development risk. Autism is a human-specific disorder. As such, the genetic cause has been implicated to highly ordered brain lateralization exhibited by humans. Two genes have been linked to autism and autism spectrum disorders (ASD): c3orf58 (a.k.a. Deleted In Autism-1 or DIA1) and cXorf36 (a.k.a.Deleted in Autism-1 Related or DIA1R).

Major depressive disorder

Major depressive disorder is a common

mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the ''Diagnostic and Stat ...

believed to be caused by irregular neural uptake of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

. While the genetic cause is unknown, genomic studies of post-mortem MDD brains have discovered abnormalities in the

fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in the ...

system which supports the theory of growth factors playing an important role in mood disorders.

Others

Other neurodegenerative disorders include

Rett syndrome Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age and almost exclusively in females. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often h ...

Prader–Willi syndrome Prader–Willi syndrome (PWS) is a genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, those affected become c ...

Angelman syndrome Angelman syndrome or Angelman's syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no f ...

, and

Williams-Beuren syndrome Williams syndrome (WS) is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed in people ...

References

External links

*http://www.yerkes.emory.edu/ *http://www.neuroscience.ox.ac.uk/ {{Genomics Genomics

Cognitive genomics testing

Approaches

Evo-geno

Evo-devo

Evo-pheno and evo-patho

Imaging genomics

Candidate gene selection

Controlling for non-genetic factors

Task selection

Species used in comparative cognitive genomics

Humans

Non-human primates

Chimpanzees

Rhesus macaques

Apes

Neurobehavioral and cognitive disorders

Down syndrome

Fragile-X syndrome

Alzheimer’s disease

Autism

Major depressive disorder

Others

See also

References

External links