MODULE 4                   ATTENTION DEFICIT-HYPERACTIVITY DISORDER

With the completion of the Human Genome Project, the location of many more genes involved in human disease are being identified. To examine human genes and genetic disorders that focus on inherited diseases select the OMIM Online Mendelian Inheritance in Man option at the NCBI homepage. This tool allows you to learn more about a disease and to understand how the disease may be inherited to offspring from parent.

Begin by searching OMIM for “Ad or “ADHD.” It is the most common childhood onset behavior disorder. It affects about 5 - 10% of children and adolescents. It is characterized with persistent inattention and/or hyperactive-impulsive behavior. ADHD results in impaired social and/or academic functioning for the child. Although many entries come up, select the one labeled “#143465 ATTENTION DEFICIT-HYPERACTIVITY DISORDER; ADHD.”

You will be linked to a page containing the clinical features, mapping, molecular genetics, and additional references on the disorder. The text begins noting that a # (number sign) is included with this disorder because evidence suggests that multiple loci contribute to the phenotype of ADHD.

What loci are associated to the susceptibility of ADHD?

At what frequency are boys more affected than girls?

What other disability occurs together with ADHD?

ADHD has been shown to be familial and heritable, in Cook’s studies.  What transporter is considered to be the primary candidate gene for ADHD? (You may need to use reference links in the Gene Mapping section.)  

Waldman’s studied the three sub-types of ADHD. What are the types?

What is the high risk gene associated with childhood ADHD?

How many base pairs long is the gene?

Are child hyperactivity-impulsivity and oppositional behaviors associated with a DAT polymorphism?

Is it important to incorporate environmental cofactors in genetic studies of ADHD? If so, what study led to this conclusion and what is the conclusion?

Display the clinical synopsis of ADHD. Name the Neuro., Misc., and Inheritance for ADHD.

What chromosome numbers have the genes for ADHD been localized?

Please answers each question on a separate sheet of paper and include the question numbers with your answers.

Module 4       ANSWERS

• ADHD1 (608903), ADHD2 (608904), ADHD3 (608905), and ADHD4 (608906).
• 8 times more frequently
• Reading disability, autism
• the dopamine transporter
• inattentive, hyperactive-impulsive, and combined
• DAT1
• 480bp
• Only when the child also had exposure to maternal prenatal smoking
• Yes.  Child hyperactivity-impulsivity and oppositional behaviors were associated with a DAT polymorphism but only when the child also had exposure to maternal prenatal smoking. Thus, it is important to incorporate environmental cofactors in genetic studies of attention deficit hyperactivity disorder.  The study, “The Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors,” by Robert S. Kahn MD, MPH, , Jane Khoury MS, William C. Nichols PhD and Bruce P. Lanphear MD, MPH.
• Clinical Synopsis - Neuro : Hyperactivity; Misc : Male:female ratio 8:1; Inheritance : Autosomal dominant
• 4, 5, 16, 17