The given sentence is missing in the paragraph below. Decide where it best fits among the options 1, 2, 3, or 4 indicated in the paragraph.

Sentence: In each of the affected males, the genetic defect was located to the X chromosome in the region of p11-12.

Paragraph: The first suggested evidence of a human genetic mutation associated with aggressive behaviour came from a study in 1993. _____(1)____. Genetic and metabolic studies were conducted on a large Dutch family in which several of the males has a syndrome of borderline mental retardation and abnormal behaviour. _____(2)____. The undesirable behaviour included impulsive aggression, arson and exhibitionism. _____(3)____. A point mutation was identified in the eighth exon of the monoamine oxidase A (MAOA) structural gene which changes glutamine to a termination codon. _____(4)____.

The correct answer is Option 4.

To determine the best position for the missing sentence, we need to analyze the logical progression of ideas and the contextual clues within the paragraph.

The missing sentence states: "In each of the affected males, the genetic defect was located to the X chromosome in the region of p11-12." This sentence provides a specific chromosomal location for a particular anomaly, referring to it as "the genetic defect." The use of the definite article "the" suggests that this genetic issue must have already been explicitly introduced in the text immediately before it.

Let us examine the flow of the paragraph leading up to blank (4):
The text first introduces a 1993 study regarding a human genetic mutation associated with aggressive behavior. It then describes the subjects of the study (a large Dutch family with affected males) and details their specific abnormal behaviors (impulsive aggression, arson, exhibitionism). Up to blank (3), the focus is entirely on the clinical description of the syndrome and the behaviors, without any mention of a specific genetic mechanism.

The sentence right before blank (4) states: "A point mutation was identified in the eighth exon of the monoamine oxidase A (MAOA) structural gene which changes glutamine to a termination codon." Here, the text finally introduces the specific genetic discovery—a point mutation.

Placing the missing sentence at blank (4) provides a perfect logical continuation. The text first identifies the specific mutation in the MAOA gene, and the missing sentence immediately follows by referring back to this exact finding as "the genetic defect," further elaborating on where this defective gene is physically mapped (the X chromosome in the region of p11-12) in the affected males.

Placing the sentence at earlier blanks, such as (1), (2), or (3), would be structurally incorrect because it would introduce "the genetic defect" prematurely, before the actual point mutation had been revealed to the reader. Therefore, position (4) is the only logical choice to maintain a coherent, step-by-step explanation of the scientific findings.