# US 8,788,215 B2 · Methods of associating an unknown biological specimen with a family > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,788,215 B2 - Document ID: US8788215B2 - Status: Granted - Kind: B2 - Application number: 13/621,311 - Filed: 2012-09-17 - Published: 2013-01-31 - Granted: 2014-07-22 - Earliest claimed: 2006-08-11 - Assignees: University of Tennessee Research Foundation - Applicants: The University of Tennessee Research Foundation - Inventors: Ranajit Chakraborty; John Douglas Birdwell; Tse-Wei Wang; Dale V. Stansberry - Web page: https://patentgrep.com/patent/US8788215B2 ## CPC - G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations - G16B 20/20: Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection - G16B 20/40: Population genetics; Linkage disequilibrium - G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY ## Abstract The present invention provides a method of predicting whether an unknown biological specimen originates from a member of a particular family. The method compares DNA profiles from at least one unknown biological specimen to DNA profiles of more than one family member, which significantly increases the methods' predictive ability. In particular, the invention describes a method of comparing test DNA profiles from unknown biological specimens to a family pedigree comprising target DNA profiles obtained from biological specimens of family members. In one embodiment, a modified Elston Stewart algorithm is used to determine a probability that a genetic relationship exists between at least one unknown biological specimen and the family pedigree. ## Claims ### Claim 1 A computer-implemented method of identifying an unknown biological specimen as hypothetically related to a family pedigree comprising at least a missing person and relationships to at least two family members having genetic information for use in a system, the system comprising a processor, a memory connected to the processor, an input for receiving a DNA profile and an output device, the computer-implemented method comprising: (a) pre-computing, via the computer processor, a portion of a pedigree likelihood ratio that a specified genetic relationship exists between a set of unknown biological specimens of a missing person and said at least two family members of the family pedigree, said family pedigree being stored in said memory and said genetic information obtained from known biological specimens of said at least two family members; (b) comparing, via the computer processor, at least three test DNA profiles obtained from the set of unknown biological specimens of the missing person to the family pedigree, a DNA profile comprising at least one DNA marker; (c) using said pre-computed pedigree likelihood ratio portion and a modified Elston Stewart algorithm, via the computer processor, to calculate a pedigree likelihood ratio that a specified genetic relationship exists between at least one unknown biological specimen of the set of unknown biological specimens and said at least two family members of the family pedigree; (d) producing a resultant set of unknown biological specimens rank-ordered according to the pedigree likelihood ratio for the family pedigree via the output device; and (e) identifying an unknown biological specimen from the rank-ordered set with a high pedigree likelihood ratio as likely corresponding to said missing person belonging in the family pedigree. ### Claim 2 (depends on 1) The method of claim 1 wherein family pedigree members' profiles comprise two DNA types selected from the group consisting of: a) STR; b) partial STR; c) Y-STR; d) SNP; e) mini-STR; and f) mitochondrial DNA. ### Claim 3 (depends on 1) The method of claim 1 wherein comparing further comprises excluding a biological specimen not compatible with the family pedigree. ### Claim 4 (depends on 1) The method of claim 1 wherein said DNA profiles obtained from the set of unknown biological specimens and genetic information about said at least two family pedigree members' profiles are stored in a database. ### Claim 5 (depends on 4) The method of claim 4 wherein the database comprises non-DNA forensic information which describes at least one unknown biological specimen. ### Claim 6 (depends on 4) The method of claim 4 wherein a DNA profile or non-DNA forensic information is used to exclude an unknown biological specimen from the resultant set of unknown biological specimens to form an updated database. ### Claim 7 (depends on 4) The method of claim 4 further comprising adding an unknown biological specimen to the set of unknown biological specimens of the database to form an updated database. ### Claim 8 (depends on 7) The method of claim 7 further comprising applying the computer-implemented method to the updated database. ### Claim 9 (depends on 4) The method of claim 4 wherein the family pedigree comprises two generations, the method comprising pre-computing the likelihood ratio portion in a recursive manner in one of a bottom-up manner from the youngest available generation up and a top-down manner from the oldest available generation down. ### Claim 10 (depends on 7) The method of claim 7 further comprising associating a test DNA profile with the added unknown biological specimen, the method comprising: (a) comparing the associated test DNA profile to a family pedigree comprising target DNA profiles obtained from biological specimens of family members; (b) using an algorithm to calculate a pedigree likelihood ratio that a specified genetic relationship exists between the associated test DNA profile and the family pedigree; and (c) identifying or excluding the added unknown biological specimen of the resultant set as likely related to the family pedigree based on the pedigree likelihood ratio. ### Claim 11 (depends on 1) The method of claim 1 further comprising using non-DNA forensic information to confirm identification of the unknown biological specimen. ### Claim 12 (depends on 11) The method of claim 11 wherein the non-DNA forensic information comprises at least one type selected from the group consisting of: a) a dental record; b) a skin marking; c) an X-ray image; d) a time of specimen collection; e) a place of specimen collection; and f) a fingerprint. ### Claim 13 (depends on 1) The method of claim 1 wherein pre-computing comprises computing a product term for available siblings of the family pedigree, the available siblings comprising the at least two family members of the family pedigree. ### Claim 14 A computer-readable medium storing computer-executable instructions for performing a computer-implemented method of identifying an unknown biological specimen as hypothetically related to a family pedigree comprising at least a missing person and relationships to at least two family members having genetic information for use in a system, the system comprising a processor, a memory connected to the processor, an input for receiving a DNA profile and an output device, the computer-implemented method comprising: (a) pre-computing, via the computer processor, a portion of a pedigree likelihood ratio that a specified genetic relationship exists between a set of unknown biological specimens of a missing person and said at least two family members of the family pedigree, said family pedigree being stored in said memory and said genetic information obtained from known biological specimens of said at least two family members; (b) comparing, via the computer processor, at least three test DNA profiles obtained from the set of unknown biological specimens of the missing person to the family pedigree, a DNA profile comprising at least one DNA marker; (c) using said pre-computed pedigree likelihood ratio portion and a modified Elston Stewart algorithm, via the computer processor, to calculate a pedigree likelihood ratio that a specified genetic relationship exists between at least one unknown biological specimen of the set of unknown biological specimens and said at least two family members of the family pedigree; (d) producing a resultant set of unknown biological specimens rank-ordered according to the pedigree likelihood ratio for the family pedigree via the output device; and (e) identifying an unknown biological specimen from the rank-ordered set with a high pedigree likelihood ratio as likely corresponding to said missing person belonging in the family pedigree. ### Claim 15 (depends on 14) The computer readable medium of claim 14 wherein comparing further comprises excluding an available or unknown biological specimen not compatible with the family pedigree. ### Claim 16 (depends on 14) The computer-readable medium of claim 14 wherein the at least two test DNA profiles comprise two DNA types selected from the group consisting of: a) STR; b) partial STR; c) Y-STR; d) SNP; e) mini-STR; and f) mitochondrial DNA. ### Claim 17 (depends on 14) The computer-readable medium of claim 14 wherein said DNA profiles from the set of unknown biological specimens and family pedigree data and genetic information obtained from biological specimens of said at least two family members are stored in a database. ### Claim 18 (depends on 17) The computer-readable medium of claim 17 wherein the DNA profiles, family pedigree data and said genetic information are stored in a plurality of databases. ### Claim 19 (depends on 17) The computer-readable medium of claim 17 wherein the database comprises non-DNA forensic information which describes at least one unknown biological specimen. ### Claim 20 (depends on 17) The computer-readable medium of claim 17 wherein a DNA profile or non-DNA forensic information is used to exclude an unknown biological specimen from the resultant set of unknown biological specimens to form an updated database. ### Claim 21 (depends on 17) The computer-readable medium of claim 17 wherein the method further comprises adding an unknown biological specimen to the database to form an updated database. ### Claim 22 (depends on 21) The computer-readable medium of claim 21 further comprising associating a test DNA profile with the added unknown biological specimen and applying the computer-implemented method to the updated database. ### Claim 23 (depends on 14) The computer-readable medium of claim 14, the method comprising repeating: (a) adding a DNA profile obtained for a different unknown biological specimen to the set of unknown biological specimens; (b) comparing an added DNA profile for the different unknown biological specimen to a family pedigree comprising target DNA profiles obtained from biological specimens of family members; (b) using the pre-computed likelihood ratio portion and an algorithm to calculate, via the computer processor, a pedigree likelihood ratio that a specified genetic relationship exists between at least one unknown biological specimen and the family pedigree; and (c) updating said resultant set of unknown biological specimens rank-ordered according to the pedigree likelihood ratio. ### Claim 24 (depends on 23) The computer readable medium of claim 23 further comprising identifying an unknown biological specimen from the rank-ordered resultant set as a missing person of the family pedigree and subsequently identifying a second unknown biological specimen as likely related to the missing person of the family pedigree. ### Claim 25 (depends on 24) The computer readable medium of claim 24 where the second unknown biological specimen is identified as a sibling of said missing person. ### Claim 26 (depends on 21) The computer readable medium of claim 21 further comprising associating a test DNA profile with the added unknown biological specimen, the method comprising: (a) comparing the associated test DNA profile to a family pedigree comprising target DNA profiles obtained from biological specimens of the at least two family members; (b) using an algorithm to calculate a pedigree likelihood ratio that a specified genetic relationship exists between the associated test DNA profile and the family pedigree; and (c) identifying or excluding the added unknown biological specimen of the resultant set as likely related to the family pedigree based on the pedigree likelihood ratio. ### Claim 27 (depends on 19) The computer-readable medium of claim 19 wherein non-DNA forensic information is utilized and the non-DNA forensic information comprises at least one type selected from the group consisting of: a) a dental record; b) a skin marking; c) an X-ray image; d) a time of specimen collection; e) a place of specimen collection; and f) a fingerprint. ### Claim 28 (depends on 14) The computer-readable medium of claim 14 wherein the said at least three test DNA profiles are neither excluded nor identified as likely related to the family pedigree based on the pedigree likelihood ratio. ### Claim 29 A computer having a processor, a memory and an output device for performing a computer-implemented method of identifying an unknown biological specimen as hypothetically related to a family pedigree comprising a missing person and at least a first, a second and a third family member, the method comprising: (a) pre-computing, via the computer processor, a portion of a pedigree likelihood ratio that a specified genetic relationship exists between a set of unknown biological specimens of a missing person and said at least two family members of the family pedigree, said family pedigree being stored in said memory and said genetic information obtained from known biological specimens of said at least two family members; (b) comparing, via the computer processor, at least three test DNA profiles obtained from the set of unknown biological specimens of the missing person to the family pedigree, a DNA profile comprising at least one DNA marker; (c) using said pre-computed pedigree likelihood ratio portion and using a modified Elston Stewart algorithm, via the computer processor, to calculate a pedigree likelihood ratio that a specified genetic relationship exists between at least one unknown biological specimen of the set of unknown biological specimens and said at least two family members of the family pedigree; (d) producing a resultant set of unknown biological specimens rank-ordered according to the pedigree likelihood ratio for the family pedigree via the output device; and (e) identifying an unknown biological specimen from the rank-ordered set with a high pedigree likelihood ratio as likely corresponding to said missing person belonging in the family pedigree. ### Claim 30 (depends on 29) The computer of claim 29 wherein the at least two test DNA profiles comprise two DNA types selected from the group consisting of: a) STR; b) partial STR; c) Y-STR; d) SNP; e) mini-STR; and f) mitochondrial DNA. ### Claim 31 (depends on 29) The computer of claim 29 wherein the at least three test DNA profiles and the family pedigree members' DNA profiles are stored in a database. ### Claim 32 (depends on 31) The computer of claim 31 wherein the database comprises non-DNA forensic information which describes at least one unknown biological specimen of the set of unknown biological specimens, the non-DNA forensic information comprising one of dental data, tattoo data, scar data, and a date of specimen collection. ### Claim 33 (depends on 32) The computer of claim 32 wherein a DNA profile or non-DNA forensic information is used to exclude an unknown biological specimen from the set of unknown biological specimens to form an updated database. ### Claim 34 (depends on 32) The computer of claim 32 further comprising adding an unknown biological specimen to the set of unknown biological specimens of the database to form an updated database. ### Claim 35 (depends on 34) The computer of claim 34 for implementing a method further comprising applying the computer implemented method to the updated database. ### Claim 36 (depends on 31) The computer of claim 31 wherein the family pedigree comprises two generations, the method comprising repeating: (a) comparing said at least three test DNA profiles from a set of unknown biological specimens to a family pedigree comprising target DNA profiles obtained from biological specimens of family members; (b) using an algorithm to calculate a likelihood function value that a genetic relationship exists between at least one unknown biological specimen and the family pedigree; and (c) excluding an unknown biological specimen having a small likelihood function value as likely related to the family. ### Claim 37 (depends on 31) The computer of claim 31 wherein the family pedigree comprises two generations, the method comprising repeating: (a) comparing said at least three test DNA profiles to a family pedigree comprising target DNA profiles obtained from biological specimens of family members; (b) using an algorithm to calculate a pedigree likelihood ratio that a specified genetic relationship exists between the test DNA profiles of, the set of unknown biological specimens and the family pedigree; and (c) either identifying or excluding said at least two test DNA profiles as likely related with the specified genetic relationship to the family pedigree based on the pedigree likelihood ratio. ### Claim 38 (depends on 35) The computer of claim 35 further comprising associating a test DNA profile with the added unknown biological specimen, the method comprising: (a) comparing the associated test DNA profile to a family pedigree comprising target DNA profiles obtained from biological specimens of family members; (b) using an algorithm to calculate a pedigree likelihood ratio that a specified genetic relationship exists between the associated test DNA profile and the family pedigree; and (c) identifying or excluding the added unknown biological specimen of the set of unknown biological specimens as likely related with the specified genetic relationship to the family pedigree based on the pedigree likelihood ratio. ### Claim 39 (depends on 36) The computer of claim 36 wherein the likelihood function value comprises a pedigree likelihood ratio and the first and second family members comprise two different family members selected from a group comprising a father, a mother, a child and a sibling of the missing person. ### Claim 40 (depends on 36) The computer of claim 36 wherein the likelihood function value comprises a probability measure for a degree of linkage of markers residing at different loci.