The only people known to be in the house on the night of JonBenét's death were her immediate family; Patsy and John Ramsey and their son Burke. The ransom note contained specific instructions against contacting police and friends, but Patsy called the police at 5:52am. She also called family and friends. 2 police officers responded to the 911 call and arrived at the Ramsey home within 3 minutes. They conducted a cursory search of the house but did not find any sign of forced entry. 

Officer Rick French went to the basement and came to a door that was secured by a wooden latch. He paused for a moment in front of the door, but walked away without opening it. Rick later explained that he was looking for an exit route used by the kidnapper, which the closed inside peg ruled out. JonBenét's body was later found behind the door. 

With JonBenét still missing, John made arrangements to pay the ransom. A forensic team was dispatched to the house. The team initially believed that the child had been kidnapped, and JonBenét's bedroom was the only room in the house that was cordoned off to prevent contamination of evidence. No precautions were taken to prevent contamination of evidence in the rest of the house. Meanwhile, friends, victim advocates, and the Ramsey family's minister arrived at the home to show support. Visitors picked up and cleaned surfaces in the kitchen, possibly destroying evidence. Boulder detective Linda Arndt arrived at about 8:00am, in anticipation of receiving further instructions by the kidnapper, but there was never an attempt by anyone to claim the money.

At 1:00pm, Detective Arndt asked John Ramsey and Fleet White, a family friend, to search the house to see if "anything seemed amiss." They started their search in the basement. John opened the latched door which Officer French had overlooked and found his daughter's body in one of the rooms. JonBenét's mouth was covered with duct tape, a nylon cord was found around her wrist and neck, and her torso was covered by a white blanket. John picked up the child's body and took it upstairs. When JonBenét was moved, the crime scene was further contaminated, and critical forensic evidence was disturbed for the returning forensic team. 

Each of the Ramseys provided handwriting, blood and hair samples to the police. John and Patsy participated in the preliminary interview for more than 2 hours, and Burke was also interviewed within the first couple of weeks following JonBenét's death.

The autopsy revealed that JonBenét had been killed by strangulation and a skull fracture. The official cause of death was "asphyxia by strangulation associated with craniocerebral trauma." There was no evidence of conventional rape, although sexual assault could not be ruled out. Although no semen was found, the was evidence that there had been a vaginal injury. At the time of the autopsy, the pathologist recorded that it appeared her vaginal area had been wiped with a cloth. Her death was ruled a homicide. 

A garrotte that was made from a length of nylon cord and the broken handle of a paintbrush was tied around JonBenét's neck and had apparently been used to strangle her. Part of the bristle end of the paintbrush was found in a tub containing Patsy's art supplies, but the bottom third of it was never found despite extensive searching of the house by the police in subsequent days. 

The autopsy revealed a "vegetable or fruit material which may represent a pineapple," which JonBenét had eaten a few hours before her death. Photographs of the home taken on the day when JonBenét's body was found show a bowl of pineapple on the kitchen table with a spoon in it. However, neither John nor Patsy said they remembered putting the bowl on the table or feeding pineapple to JonBenét. Police reported that they found JonBenét's 9 year old brother Burke Ramsey's fingerprints on the bowl. The Ramseys have always said that Burke slept through the entire night until he was awakened several hours after the police arrived.

In December 2003, forensic investigators extracted enough material from a mixed blood sample found on JonBenét's underwear to establish a DNA profile. That DNA belonged to an unknown male person, and excluded the DNA of each of the Ramseys. The DNA was submitted to the FBI's Combined DNA Index System (CODIS), a database containing more than 1.6 million DNA profiles, but the sample did not match any profile in the database. In October 2016, a report said that new forensic analysis with more sensitive techniques revealed that the original DNA contained genetic markers from 2 individuals other than JonBenét. 

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